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  • 101.
    Lövdén, Martin
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Max Planck Inst Human Dev, Ctr Lifespan Psychol, Berlin, Germany.
    Laukka, Erika Jonsson
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Rieckmann, Anna
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Kalpouzos, Grégoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Li, Tie-Qiang
    Karolinska Inst, Dept Med Phys, S-11330 Stockholm, Sweden .
    Jonsson, Tomas
    Karolinska Inst, Dept Med Phys, S-11330 Stockholm, Sweden .
    Wahlund, Lars-Olof
    Karolinska Inst, Dept Clin Geriatr, S-11330 Stockholm, Sweden.
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontol Res Ctr, Stockholm, Sweden.
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    The dimensionality of between-person differences in white matter microstructure in old age2013In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 34, no 6, p. 1386-1398Article in journal (Refereed)
    Abstract [en]

    Between-person differences in white matter microstructure may partly generalize across the brain and partly play out differently for distinct tracts. We used diffusion-tensor imaging and structural equation modeling to investigate this issue in a sample of 260 adults aged 60–87 years. Mean fractional anisotropy and mean diffusivity of seven white matter tracts in each hemisphere were quantified. Results showed good fit of a model positing that individual differences in white matter microstructure are structured according to tracts. A general factor, although accounting for variance in the measures, did not adequately represent the individual differences. This indicates the presence of a substantial amount of tract-specific individual differences in white matter microstructure. In addition, individual differences are to a varying degree shared between tracts, indicating that general factors also affect white matter microstructure. Age-related differences in white matter microstructure were present for all tracts. Correlations among tract factors did not generally increase as a function of age, suggesting that aging is not a process with homogenous effects on white matter microstructure across the brain. These findings highlight the need for future research to examine whether relations between white matter microstructure and diverse outcomes are specific or general. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.

  • 102. Maass, Anne
    et al.
    Düzel, Sandra
    Brigadski, Tanja
    Goerke, Monique
    Becke, Andreas
    Sobieray, Uwe
    Neumann, Katja
    Lövdén, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Max Planck Institute for Human Development, Germany.
    Lindenberger, Ulman
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Braun-Dullaeus, Rüdiger
    Ahrens, Dörte
    Heinze, Hans-Jochen
    Müller, Notger G.
    Lessmann, Volkmar
    Sendtner, Michael
    Düzel, Emrah
    Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults2016In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 131, p. 142-154Article in journal (Refereed)
    Abstract [en]

    Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77 years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here.

  • 103. 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.

  • 104.
    Malke, Zelga
    Stockholm University, Faculty of Science, Department of Physics.
    System for dose audit for external radiation therapy based on EPR dosimetry with Lithium Formate2010Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Radiation therapy is an important method to treat cancer with the aim to deliver as high doses as reasonably achievable to the tumor while protecting the surrounding healthy tissue and organs at risk, OARs. Therefore, it is essential to have high accuracy in the dose delivered clinically and quality assurances are required. In the meantime, radiation therapy techniques are becoming more advanced and complex, introducing a significant risk of random and systematic errors that needs to be investigated. Hence, the need of independent dose verifications has increased. The purpose of the present work is to design and create a mailed audit system for external evaluation of the dose to water in relevant points in a phantom, including influences from the whole treatment chain, from computed tomography, CT, scanning, to contouring of structures, treatment planning and treatment delivery.

    The measurements were performed using an anthropomorphic Polymethyl methacrylate, PMMA, phantom designed to be relevant for the head-and-neck region containing inserts corresponding to tumour, salivary glands and medulla made of PMMA and that are easily distinguishable from the surroundings for contouring. Inhomogeneities of both Teflon, corresponding to the spinal cord, and air were also included. Pellet shaped electron paramagnetic resonance, EPR, dosimeters made of lithium formate with a diameter of 4.5 mm and height of 5 mm were made for the measurements. The dosimeters can be placed in various positions in the different structures of the phantom using PMMA tubes and can be analyzed using a spectrometer.

    In order to test the precision and accuracy of the EPR dosimetry method, measurements with three blind tests were performed simultaneously with an ionization chamber for comparison of absorbed doses. For the audit measurement, the audit phantom was CT scanned twice both with a Siemens CT scan and GE (General Electric)) CT scan for comparison of Hounsfield Units, HU, and dose distributions. The target and the OARs were contoured in the treatment planning system, TPS, (Varian, Eclipse) and a dynamic Intensity modulated radiation therapy, IMRT, treatment plan was created. The treatment plan consisted of seven coplanar 6 MV fields giving the target a dose of 5 Gy delivered with a Varian, Clinac iX accelerator. The absorbed doses to water were determined in seven locations: three points in the target, one in each parotis, one in the medulla and one in the air cavity. The absorbed doses were determined using the signal from the EPR dosimeters and were compared to the planned doses. Also, the measured and reconstructed volumes of the structures were compared.

    The blind tests doses obtained from the EPR dosimeters agreed with the results obtained from the ionization chamber within 1% and are well below the calculated uncertainties (1 SD) in the EPR measurements. The absorbed doses and the dose distributions were not affected by any spread in HU and the absorbed doses had an agreement within 0.5% in comparison between the Siemens and GE CT studies. The determined doses agreed with planned doses within 4% for all the structures except the air cavity. This deviation is not covered by the calculated standard uncertainty. However, the deviation does fall within two standard deviations, corresponding to a confidence interval of 95%. Also the measured and planned volumes had an agreement within 2.5% for smaller structures and within 5% for larger structures.

    Repeating the whole measurement chain with other dosimeter batches is required using two or three dosimeters in each measurement point for higher precision. A conclusion can be made that this work showed promising initial results for an audit system for evaluation of the dose to water in relevant points in a phantom, including influences from the whole treatment chain.

  • 105.
    Marklund, Petter
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Context dependent switching between proactive and reactive working memory control mechanisms in the right inferior frontal gyrus2012In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 63, no 3, p. 1552-1560Article in journal (Refereed)
    Abstract [en]

    A critical feature of higher cognitive functioning is the capacity to flexibly tailor information processing and behaviors to current situational demands. Recent neurocognitive models have been postulated to account for the dynamic nature of human executive processing by invoking two dissociable cognitive control modes, proactive and reactive control. These may involve partially overlapping, but temporally distinct neural implementation in the prefrontal cortex. Prior brain imaging studies exploring proactive control have mainly used tasks requiring only information about single-items to be retained over unfilled delays. Whether proactive control can also be utilized to facilitate performance in more complex working memory tasks, in which concurrent processing of intervening items and updating is mandatory during contextual cue maintenance remains an open question. To examine this issue and to elucidate the extent to which overlapping neural substrates underlie proactive and reactive control we used fMRI and a modified verbal 3-back paradigm with embedded cues predictive of high-interference trials. This task requires context information to be retained over multiple intervening trials. We found that performance improved with item-specific cues predicting forthcoming lures despite increased working memory load. Temporal dynamics of activation in the right inferior frontal gyrus suggest flexible switching between proactive and reactive control in a context-dependent fashion, with greater sustained responses elicited in the 3-back task involving context maintenance of cue information and greater transient responses elicited in the 3-back task absent of cues.

  • 106.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Costa Ferreira, B
    Shi, C
    Lind, B K
    Papanikolaou, N
    Comparison of the 3D-conformal, helical tomotherapy and multileaf collimators-based intensity modulated radiotherapy modalities using radiobiological measures.In: Journal of B.U.ON. : official journal of the Balkan Union of Oncology, ISSN 1107-0625, Vol. 13, no 1, p. 75-86Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Intensity modulated radiotherapy (IMRT) using multileaf collimators (MLC) and helical tomotherapy (HT) have become increasingly popular over the past few years. However, their clinical efficacy and effectiveness continue to be investigated. In order to provide a more thorough evaluation and comparison of treatment plans, the utilization of the biologically effective uniform dose (D) together with the complication-free tumor control probability (P(+)) are examined. MATERIALS AND METHODS: In this study, a typical case of lung cancer was investigated by developing a 3D conformal treatment plan, a linac MLC-based step-and-shoot IMRT plan and a HT plan. The 3 different treatment plans were compared based on radiobiological measures by using the P(+) index and the D concept as the common prescription point of the plans and plotting the tissue response probabilities vs. D for a range of prescription doses. RESULTS: The applied plan evaluation method showed that in this lung cancer case the MLC-based IMRT plan was best over the clinically useful dose prescription range. The 3D-conformal, MLC-based IMRT and HT treatment plans gave a P(+) of 55.4%, 72.9% and 66.9%, for a D to the internal target volume (ITV) of 57.0 Gy, 66.9 Gy and 64.0 Gy, respectively. CONCLUSION: In comparison to 3D conformal radiotherapy, both MLC based-IMRT and HT can better encompass the often large ITV required while minimizing the volume of the organs at risk receiving high dose. Taking into account the dose-response relations of the irradiated tumors and normal tissues, a radiobiological treatment plan evaluation can be performed, which may provide a closer association of the delivered treatment with the clinical outcome.

  • 107.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Department of Radiation Oncology, University of Texas Health Sciences Center at San Antonio, Texas.
    Ferreira, Brigida Costa
    Papanikolaou, Nikos
    Lopes, Maria do Carmo
    Analysis of fractionation correction methodologies for multiple phase treatment plans in radiation therapy2013In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 40, no 3, p. 031715-Article in journal (Refereed)
    Abstract [en]

    Purpose: Radiation therapy is often delivered by multiple sequential treatment plans. For an accurate radiobiological evaluation of the overall treatment, fractionation corrections to each dose distribution must be applied before summing the three-dimensional dose matrix of each plan since the simpler approach of performing the fractionation correction to the total dose-volume histograms, obtained by the arithmetical sum of the different plans, becomes inaccurate for more heterogeneous dose patterns. In this study, the differences between these two fractionation correction methods, named here as exact (corrected before) and approximate (after summation), respectively, are assessed for different cancer types. Methods: Prostate, breast, and head and neck (HN) tumor patients were selected to quantify the differences between two fractionation correction methods (the exact vs the approximate). For each cancer type, two different treatment plans were developed using uniform (CRT) and intensity modulated beams (IMRT), respectively. The responses of the target and normal tissue were calculated using the Poisson linear-quadratic-time model and the relative seriality model, respectively. All treatments were radiobiologically evaluated and compared using the complication-free tumor control probability (P+), the biologically effective uniform dose ((D) double under bar) together with common dosimetric criteria. Results: For the prostate cancer patient, an underestimation of around 14%-15% in P+ was obtained when the fractionation correction was applied after summation compared to the exact approach due to significant biological and dosimetric variations obtained between the two fractionation correction methods in the involved lymph nodes. For the breast cancer patient, an underestimation of around 3%-4% in the maximum dose in the heart was obtained. Despite the dosimetric differences in this organ, no significant variations were obtained in treatment outcome. For the HN tumor patient, an underestimation of about 5% in treatment outcome was obtained for the CRT plan as a result of an underestimation of the planning target volume control probability by about 10%. An underestimation of about 6% in the complication probability of the right parotid was also obtained. For all the other organs at risk, dosimetric differences of up to 4% were obtained but with no significant impact in the expected clinical outcome. However, for the IMRT plan, an overestimation in P+ of 4.3% was obtained mainly due to an underestimation of the complication probability of the left and right parotids (2.9% and 5.8%, respectively). Conclusions: The use of the exact fractionation correction method, which is applying fractionation correction on the separate dose distributions of a multiple phase treatment before their summation was found to have a significant expected clinical impact. For regions of interest that are irradiated with very heterogeneous dose distributions and significantly different doses per fraction in the different treatment phases, the exact fractionation correction method needs to be applied since a significant underestimation of the true patient outcome can be introduced otherwise.

  • 108.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Ferreira, Brigida Costa
    Shi, Chengyu
    Delichas, Miltiadis G
    Lind, Bengt K
    Papanikolaou, Nikos
    Comparison of the helical tomotherapy and MLC-based IMRT radiation modalities in treating brain and cranio-spinal tumors.2009In: Technology in Cancer Research & Treatment (Trykt), ISSN 1533-0346, E-ISSN 1533-0338, Vol. 8, no 1, p. 3-14Article in journal (Refereed)
    Abstract [en]

    The investigation of the clinical efficacy and effectiveness of Intensity Modulated Radiotherapy (IMRT) using Multileaf Collimators (MLC) and Helical Tomotherapy (HT) has been an issue of increasing interest over the past few years. In order to assess the suitability of a treatment plan, dosimetric criteria such as dose-volume histograms (DVH), maximum, minimum, mean, and standard deviation of the dose distribution are typically used. Nevertheless, the radiobiological parameters of the different tumors and normal tissues are often not taken into account. The use of the biologically effective uniform dose (D=) together with the complication-free tumor control probability (P(+)) were applied to evaluate the two radiation modalities. Two different clinical cases of brain and cranio-spinal axis cancers have been investigated by developing a linac MLC-based step-and-shoot IMRT plan and a Helical Tomotherapy plan. The treatment plans of the MLC-based IMRT were developed on the Philips treatment planning station using the Pinnacle 7.6 software release while the dedicated Tomotherapy treatment planning station was used for the HT plan. With the use of the P(+) index and the D(=) concept as the common prescription point, the different treatment plans were compared based on radiobiological measures. The tissue response probabilities were plotted against D(=) for a range of prescription doses. The applied plan evaluation method shows that in the brain cancer, the HT treatment gives slightly better results than the MLC-based IMRT in terms of optimum expected clinical outcome (P(+) of 66.1% and 63.5% for a D(=) to the PTV of 63.0 Gy and 62.0 Gy, respectively). In the cranio-spinal axis cancer, the HT plan is significantly better compared to the MLC-based IMRT plan over the clinically useful dose prescription range (P(+) of 84.1% and 28.3% for a D(=) to the PTV of 50.6 Gy and 44.0 Gy, respectively). If a higher than 5% risk for complications could be allowed, the complication-free tumor control could be increased by almost 30% compared to the initial dose prescription. In comparison to MLC based-IMRT, HT can better encompass the often large PTV while minimizing the volume of the OARs receiving high dose. A radiobiological treatment plan evaluation can provide a closer association of the delivered treatment with the clinical outcome by taking into account the dose-response relations of the irradiated tumors and normal tissues. The use of P - (D=) diagrams can complement the traditional tools of evaluation such as DVHs, in order to compare and effectively evaluate different treatment plans.

  • 109.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Department of Physics. University of North Carolina, United States; Karolinska Institutet, Sweden.
    Komisopoulos, Georgios
    Buckey, Courtney
    Mavroeidi, Margarita
    Swanson, Gregory P.
    Baltas, Dimos
    Papanikolaou, Nikos
    Stathakis, Sotirios
    Radiobiological evaluation of prostate cancer IMRT and conformal-RT plans using different treatment protocols2017In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 40, p. 33-41Article in journal (Refereed)
    Abstract [en]

    The purpose of this study is to evaluate the clinical efficacy of both step-and-shoot IMRT and 3D-Conformal Radiation Therapy modalities (CRT) in treating prostate cancer using radiobiological measures. Another aim was to estimate the risks for developing secondary malignancies in bladder and rectum due to radiotherapy from the corresponding modalities. The treatment plans of ten prostate cancer patients were developed using IMRT and CRT. For the IMRT plans, two beam energies and two treatment protocols were used (the RTOG 0415 and a most restrictive one proposed by Fox Chase Cancer Center (FCCC)). For the evaluation of these plans, the complication-free tumor control probability, the total probability of injury, the total probability of control/benefit, and the biologically effective uniform dose were employed. Furthermore, based on the dosimetric data of IMRT and CRT, the risk for secondary malignancies was calculated for bladder and rectum. The average risk for secondary malignancy was lower for the bladder (0.37%) compared to the rectum (0.81%) based on all the treatment plans of the ten prostate cancer patients. The highest average risk for secondary malignancy for bladder and rectum was for the CRT-6X modality (0.46% and 1.12%, respectively) and the lowest was for the IMRT RTOG-18X modality (0.33% and 0.56%, respectively). The > Grade 2 LENT/SOMA response probability was lower for the bladder than for the rectum in all the plans. For the bladder the highest average value was for the IMRT RTOG-18X (0.9%) and the lowest was for the CRT-18X modality (0.1%). For the rectum, the highest average value was for the IMRT RTOG-6X (11.9%) and the lowest was for the IMRT FCCC-18X modality (2.2%). By using radiobiological measures it is shown that the IMRT FCCC plans had the lowest risks for normal tissue complications, whereas the IMRT RTOG had the highest. Regarding the risk for secondary malignancies, the CRT plans showed the highest values for both bladder and rectum.

  • 110.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Komisopoulos, Georgios
    Lind, Bengt K
    Papanikolaou, Nikos
    Interpretation of the dosimetric results of three uniformity regularization methods in terms of expected treatment outcome.2008In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 35, no 11, p. 5009-18Article in journal (Refereed)
    Abstract [en]

    In IMRT treatment plan optimization there are various methods that try to regularize the variation of dose nonuniformity using purely dosimetric measures. However, although these methods can help in finding a good dose distribution, they do not provide any information regarding the expected treatment outcome. When a treatment plan optimization is performed using biological measures, the final goal should be some indication about the expected tumor control or normal tissue complications, which is the primary goal of treatment planning (the association of treatment configurations and dose prescription with the treatment outcome). In this study, this issue is analyzed distinguishing the dose-oriented treatment plan optimization from the response-oriented optimization. Three different dose distributions were obtained by using a dose-based optimization technique, an EUD-based optimization without applying any technique for regularizing the nonuniformity of the dose distribution, and an EUD-based optimization using a variational regularization technique, which controls dose nonuniformity. The clinical effectiveness of the three dose distributions was investigated by calculating the response probabilities of the tumors and organs-at-risk (OARs) involved in two head and neck and prostate cancer cases. The radiobiological models used are the linear-quadratic-Poisson and the Relative Seriality models. Furthermore, the complication-free tumor control probability and the biologically effective uniform dose (D) were used for treatment plan evaluation and comparison. The radiobiological comparison shows that the EUD-based optimization using L-curve regularization gives better results than the EUD-based optimization without regularization and dose-based optimization in both clinical cases. Concluding, it appears that the applied dose nonuniformity regularization technique is expected to improve the effectiveness of the optimized IMRT dose distributions. However, more patient cases are needed to validate the statistical significance of the results and conclusions presented in this paper.

  • 111.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institute, Sweden.
    Milickovic, Natasa
    Cruz, Wilbert F.
    Tselis, Nikolaos
    Karabis, Andreas
    Stathakis, Sotirios
    Papanikolaou, Nikos
    Zamboglou, Nikolaos
    Baltas, Dimos
    Comparison of Different Fractionation Schedules Toward a Single Fraction in High-Dose-Rate Brachytherapy as Monotherapy for Low-Risk Prostate Cancer Using 3-Dimensional Radiobiological Models2014In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 88, no 1, p. 216-223Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of the present study was the investigation of different fractionation schemes to estimate their clinical impact. For this purpose, widely applied radiobiological models and dosimetric measures were used to associate their results with clinical findings. Methods and Materials: The dose distributions of 12 clinical high-dose-rate brachytherapy implants for prostate were evaluated in relation to different fractionation schemes. The fractionation schemes compared were: (1) 1 fraction of 20 Gy; (2) 2 fractions of 14 Gy; (3) 3 fractions of 11 Gy; and (4) 4 fractions of 9.5 Gy. The clinical effectiveness of the different fractionation schemes was estimated through the complication-free tumor control probability (P (+)), the biologically effective uniform dose, and the generalized equivalent uniform dose index. Results: For the different fractionation schemes, the tumor control probabilities were 98.5% in 1 x 20 Gy, 98.6% in 2 x 14 Gy, 97.5% in 3 x 11 Gy, and 97.8% in 4 x 9.5 Gy. The corresponding P+ values were 88.8% in 1 x 20 Gy, 83.9% in 2 x 14 Gy, 86.0% in 3 x 11 Gy, and 82.3% in 4 x 9.5 Gy. With use of the fractionation scheme 4 x 9.5 Gy as reference, the isoeffective schemes regarding tumor control for 1, 2, and 3 fractions were 1 x 19.68 Gy, 2 x 13.75 Gy, and 3 x 11.05 Gy. The optimum fractionation schemes for 1, 2, 3, and 4 fractions were 1 x 19.16 Gy with a P+ of 91.8%, 2 x 13.2 Gy with a P+ of 89.6%, 3 x 10.6 Gy with a P+ of 88.4%, and 4 x 9.02 Gy with a P+ of 86.9%. Conclusions: Among the fractionation schemes 1 (+) 20 Gy, 2 (+) 14 Gy, 3 x 11 Gy, and 4 x 9.5 Gy, the first scheme was more effective in terms of P+. After performance of a radiobiological optimization, it was shown that a single fraction of 19.2 to 19.7 Gy (average 19.5 Gy) should produce at least the same benefit as that given by the 4 x 9.5 Gy scheme, and it should reduce the expected total complication probability by approximately 40% to 55%.

  • 112.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Shi, C.
    Plataniotis, G. A.
    Delichas, M. G.
    Costa Ferreira, B.
    Rodriguez, S.
    Lind, B. K.
    Stockholm University, Faculty of Science, Department of Physics.
    Papanikolaou, N.
    Comparison of the helical tomotherapy against the multileaf collimator-based intensity-modulated radiotherapy and 3D conformal radiation modalities in lung cancer radiotherapy2011In: British Journal of Radiology, ISSN 0007-1285, E-ISSN 1748-880X, Vol. 84, no 998, p. 161-172Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this study was to compare three-dimensional (3D) conformal radiotherapy and the two different forms of IMRT in lung cancer radiotherapy. Methods: Cases of four lung cancer patients were investigated by developing a 3D conformal treatment plan, a linac MLC-based step-and-shoot IMRT plan and an HT plan for each case. With the use of the complication-free tumour control probability (P(+)) index and the uniform dose concept as the common prescription point of the plans, the different treatment plans were compared based on radiobiological measures. Results: The applied plan evaluation method shows the MLC-based IMRT and the HT treatment plans are almost equivalent over the clinically useful dose prescription range; however, the 3D conformal plan inferior. At the optimal dose levels, the 3D conformal treatment plans give an average P(+) of 48.1% for a effective uniform dose to the internal target volume (ITV) of 62.4 Gy, whereas the corresponding MLC-based IMRT treatment plans are more effective by an average Delta P(+) of 27.0% for a D effective uniform dose of 16.3 Gy. Similarly, the HT treatment plans are more effective than the 3D-conformal plans by an average Delta P(+) of 23.8% for a Delta effective uniform dose of 11.6 Gy. Conclusion: A radiobiological treatment plan evaluation can provide a closer association of the delivered treatment with the clinical outcome by taking into account the dose-response relations of the irradiated tumours and normal tissues. The use of P - effective uniform dose diagrams can complement the traditional tools of evaluation to compare and effectively evaluate different treatment plans.

  • 113.
    Mavroidis, Panayiotis
    et al.
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Stathakis, Sotirios
    Gutierrez, Alonso
    Esquivel, Carlos
    Shi, Chenyu
    Papanikolaou, Nikos
    Expected clinical impact of the differences between planned and delivered dose distributions in helical tomotherapy for treating head and neck cancer using helical megavoltage CT images.2009In: Journal of applied clinical medical physics / American College of Medical Physics, ISSN 1526-9914, Vol. 10, no 3, p. 2969-Article in journal (Refereed)
    Abstract [en]

    Helical Tomotherapy (HT) has become increasingly popular over the past few years. However, its clinical efficacy and effectiveness continues to be investigated. Pre-treatment patient repositioning in highly conformal image-guided radiation therapy modalities is a prerequisite for reducing setup uncertainties. A MVCT image set has to be acquired to account for daily changes in the patient's internal anatomy and setup position. Furthermore, a comparison should be performed to the kVCT study used for dosimetric planning, by a registration process which results in repositioning the patient according to specific transitional and rotational shifts. Different image registration techniques may lead to different repositioning of the patient and, as a result, to varying delivered doses. This study aims to investigate the expected effect of patient setup correction using the Hi-Art tomotherapy system by employing radiobiological measures such as the biologically effective uniform dose (BEUD) and the complication-free tumor control probability (P+). In this study, a typical case of lung cancer with metastatic head & neck disease was investigated by developing a Helical Tomotherapy plan. For the Tomotherapy HiArt plan, the dedicated Tomotherapy treatment planning station was used. Three dose distributions (planned and delivered with and without patient setup correction) were compared based on radiobiological measures by using the P+ index and the BEUD concept as the common prescription point of the plans and plotting the tissue response probabilities against the mean target dose for a range of prescription doses. The applied plan evaluation method shows that in this cancer case the planned and delivered dose distributions with and without patient setup correction give a P+ of 81.6%, 80.9% and 72.2%, for a BEUD to the planning target volume (PTV) of 78.0Gy, 77.7Gy and 75.4Gy, respectively. The corresponding tumor control probabilities are 86.3%, 85.1% and 75.1%, whereas the total complication probabilities are 4.64%, 4.20% and 2.89%, respectively. HT can encompass the often large PTV required while minimizing the volume of the organs at risk receiving high dose. However, the effectiveness of a HT treatment plan can be considerably deteriorated if an accurate patient setup system is not available. Taking into account the dose-response relations of the irradiated tumors and normal tissues, a radiobiological treatment plan evaluation can be performed, which may provide a closer association of the delivered treatment with the clinical outcome. In such situations, for effective evaluation and comparison of different treatment plans, traditional dose based evaluation tools can be complemented by the use of P+,BEUD diagrams.

  • 114. Nagel, Irene E
    et al.
    Preuschhof, Claudia
    Li, Shu-Chen
    Nyberg, Lars
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lindenberger, Ulman
    Heekeren, Hauke R
    Load modulation of BOLD response and connectivity predicts working memory performance in younger and older adults2011In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 23, no 8, p. 2030-2045Article in journal (Refereed)
    Abstract [en]

    Individual differences in working memory (WM) performance have rarely been related to individual differences in the functional responsivity of the WM brain network. By neglecting person-to-person variation, comparisons of network activity between younger and older adults using functional imaging techniques often confound differences in activity with age trends in WM performance. Using functional magnetic resonance imaging, we investigated the relations among WM performance, neural activity in the WM network, and adult age using a parametric letter n-back task in 30 younger adults (21-31 years) and 30 older adults (60-71 years). Individual differences in the WM network's responsivity to increasing task difficulty were related to WM performance, with a more responsive BOLD signal predicting greater WM proficiency. Furthermore, individuals with higher WM performance showed greater change in connectivity between left dorsolateral prefrontal cortex and left premotor cortex across load. We conclude that a more responsive WM network contributes to higher WM performance, regardless of adult age. Our results support the notion that individual differences in WM performance are important to consider when studying the WM network, particularly in age-comparative studies.

  • 115. Nakamura, Ayumi
    et al.
    Monzen, Satoru
    Takasugi, Yuki
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Mariya, Yasushi
    Application of cell sorting for enhancing the performance of the cytokinesis-block micronucleus assay2016In: Journal of radiation research, ISSN 0449-3060, E-ISSN 1349-9157, Vol. 57, no 2, p. 121-126Article in journal (Refereed)
    Abstract [en]

    Among the numerous methods available to assess genotoxicity, the cytokinesis-block micronucleus (CBMN) assay is very popular due its relative simplicity and power to detect both clastogenic and aneugenic compounds. A problem with the CBMN assay is that all DNA damaging agents also inhibit the ability of cells to progress through mitosis, leading to a low number of binucleated cells (BNCs). One method to resolve this issue is to ensure a sufficient proportion of BNCs in the samples. In the current study, the applicability of a cell sorting system capable of isolating cell fractions containing abundant BNCs was investigated. Furthermore, to investigate the relationship between the cell division delay due to radiation exposure and the generation of BNCs and micronuclei (MN), we assessed a series of lag times between radiation exposure and addition of cytochalasin-B (Cyt-B). Cells from the human chronic myelogenous leukemia cell line K562 were exposed to X-rays (2 Gy and 4 Gy), and Cyt-B was subsequently added at 0, 6 and 12 h following irradiation. After treatment with Cyt-B for 24 h, the percentage of BNCs, the MN frequency and the cell cycle distribution were analyzed. In addition, cells displaying the DNA contents corresponding to BNCs were isolated and analyzed. The results indicate that applying the cell sorter to the CBMN assay increased the percentage of BNCs compared with the standard method. Thus, this technique is a promising way of enhancing the capacity of the CBMN assay.

  • 116. Nielsen, Steffen
    et al.
    Bassler, Niels
    Stockholm University, Faculty of Science, Department of Physics.
    Grzanka, Leszek
    Swakon, Jan
    Olko, Pawel
    Andreassen, Christian Nicolaj
    Alsner, Jan
    Sørensen, Brita Singers
    Optimal reference genes for normalization of qPCR gene expression data from proton and photon irradiated dermal fibroblasts2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 12688Article in journal (Refereed)
    Abstract [en]

    The transcriptional response of cells exposed to proton radiation is not equivalent to the response induced by traditional photon beams. Changes in cellular signalling is most commonly studied using the method Quantitative polymerase chain reaction (qPCR). Stable reference genes must be used to accurately quantify target transcript expression. The study aim was to identify suitable reference genes for normalisation of gene expression levels in normal dermal fibroblasts irradiated with either proton or photon beams. The online tool RefFinder was used to analyse and identify the most stably expressed genes from a panel of 22 gene candidates. To assess the reliability of the identified reference genes, a selection of the most and least stable reference genes was used to normalise target transcripts of interest. Fold change levels varied considerably depending on the used reference gene. The top ranked genes IPO8, PUM1, MRPL19 and PSMC4 produced highly similar target gene expression, while expression using the worst ranked genes, TFRC and HPRT1, was clearly modified due to reference gene instability.

  • 117.
    Nilsson, Bo N.
    Stockholm University, Faculty of Science, Department of Physics.
    Exrcises with solutions in radiation physics2015Book (Other academic)
    Abstract [en]

    This material is intended for use in courses in radiation physics. Many textbooks include exercises, but not often full solutions, and they often refer to specific material in the textbook. This material can be used in many courses, often included in a medical physics graduate program, independent of a specific textbook. The material consists of six chapters covering the basic fundamental radiation physics, but not the more specific clinical applications where there is a rapid change and in which the exercises may be obsolete after some time. The first chapter includes exercises related to radioactive sources and decay schemes. This is followed by a chapter covering the interaction of ionizing radiation, including photons and charged particles. The text then continues with a chapter on detectors and measurements including both some simple counting statistics and properties of detectors. The next chapter is dedicated to dosimetry, which is a major subject in medical physics. A short chapter is covering radiobiology, where there is a focus on different cell survival models. The last chapter is dealing with radiation protection and health physics. Both radiation shielding calculations and radioecology are covered. The exercises in the material have been used in the education for medical physicists in Stockholm, Sweden, and the order of chapters follows the order of courses in this education, but hopefully they are useful in all applications of radiation physics including also health physics. Some problems are probably similar to what can be found in other material as there are some items that are always important to include in the courses and when producing exercises it is easy to forget where any idea is coming from.

  • 118.
    Nilsson, Johan
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Accurate description of heterogeneous tumors for biologically optimized radiation therapy2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis, a model of tissue oxygenation is presented, that takes into account the heterogeneous nature of tumor vasculature. Even though the model is rather simple, the resulting oxygen distributions agree very well with clinically observed oxygen distributions for most tumors and healthy normal tissues. The model shows that the vascular density may not describe the oxygenation of a tissue sufficiently well, unless the heterogeneity of the vascular system is taken into account. Based on the oxygen distributions from the tissue model, the associated radiation response at low and high doses can be determined.

    The radiation response of heterogeneous tumors should preferably be described by two clonogen compartments, one resistant and one sensitive, dominating the response at high and low radiation doses, respectively. Furthermore, each compartment should be characterized by the effective radiation resistance and the effective clonogen number. The resistant-sensitive model of radiation response has been analyzed in great detail. It accurately describes the response of severely heterogeneous tumors, both at low and high doses and LET values. The effective response parameters are given as integrals, averaged over the whole spectrum of radiation resistance. The parameters can also be determined from clinically established dose-response relations.

    The main properties of the dose-response relation for a generally heterogeneous tumor is described in some detail. The normalized dose-response gradient has been generalized to take heterogeneities in both dose delivery and radiation response into account. This quantity is important for accurate treatment plan optimization using intensity modulated radiation therapy for individual patients.

  • 119. Niskanen, Eini
    et al.
    Könönen, Mervi
    Määttä, Sara
    Hallikainen, Merja
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Casarotto, Silvia
    Massimini, Marcello
    Vanninen, Ritva
    Mervaala, Esa
    Karhu, Jari
    Soininen, Hilkka
    New insights into Alzheimer's disease progression: a combined TMS and structural MRI study2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 10, p. 1-8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Combination of structural and functional data of the human brain can provide detailed information of neurodegenerative diseases and the influence of the disease on various local cortical areas.

    METHODOLOGY AND PRINCIPAL FINDINGS: To examine the relationship between structure and function of the brain the cortical thickness based on structural magnetic resonance images and motor cortex excitability assessed with transcranial magnetic stimulation were correlated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients as well as in age-matched healthy controls. Motor cortex excitability correlated negatively with cortical thickness on the sensorimotor cortex, the precuneus and the cuneus but the strength of the correlation varied between the study groups. On the sensorimotor cortex the correlation was significant only in MCI subjects. On the precuneus and cuneus the correlation was significant both in AD and MCI subjects. In healthy controls the motor cortex excitability did not correlate with the cortical thickness.

    CONCLUSIONS: In healthy subjects the motor cortex excitability is not dependent on the cortical thickness, whereas in neurodegenerative diseases the cortical thinning is related to weaker cortical excitability, especially on the precuneus and cuneus. However, in AD subjects there seems to be a protective mechanism of hyperexcitability on the sensorimotor cortex counteracting the prominent loss of cortical volume since the motor cortex excitability did not correlate with the cortical thickness. Such protective mechanism was not found on the precuneus or cuneus nor in the MCI subjects. Therefore, our results indicate that the progression of the disease proceeds with different dynamics in the structure and function of neuronal circuits from normal conditions via MCI to AD.

  • 120. Nordenskjöld, A. C.
    et al.
    Palme, Mårten
    Stockholm University, Faculty of Social Sciences, Department of Economics.
    Kaijser, M.
    X-ray exposure in utero and school performance: a population-based study of X-ray pelvimetry2015In: Clinical Radiology, ISSN 0009-9260, E-ISSN 1365-229X, Vol. 70, no 8, p. 830-834Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate the association between exposure to ionising radiation from pelvimetric examinations in utero and school performance. MATERIAL AND METHODS: This was a population-based cohort study comprising 46,066 children born in the county of Ostergotland, Sweden, from 1980 through 1990. Through record linkage between Swedish registers, children exposed in utero to X-ray pelvimetry examination were compared to other children born in the same county during the study period, as well as to their unexposed siblings. Outcome variable was primary school grades, expressed in centiles and calculated through linear regression. RESULTS: In the univariate analysis, children exposed to X-ray pelvimetry in utero had higher school grades compared to unexposed children (point estimate 3 centiles, 95% confidence interval [CI]: 1.5 to 4.6). When sex, mother's education and income, birth order, and birth position were included in the analysis; however, the difference was reduced and the association was no longer statistically significant (PE 1.4, 95% CI: -0.1 to 2.8). Comparing exposed children with their siblings showed no statistical difference in univariate analysis or in multivariate analysis. CONCLUSION: No suggestion was found of a negative effect on school performance from in utero exposure of diagnostic X-ray pelvimetry.

  • 121. Oestreicher, Ursula
    et al.
    Samaga, Daniel
    Ainsbury, Elizabeth
    Antunes, Ana Catarina
    Baeyens, Ans
    Barrios, Leonardo
    Beinke, Christina
    Beukes, Philip
    Blakely, William F.
    Cucu, Alexandra
    De Amicis, Andrea
    Depuydt, Julie
    De Sanctis, Stefania
    Di Giorgio, Marina
    Dobos, Katalin
    Dominguez, Inmaculada
    Pham, Ngoc
    Espinoza, Marco E.
    Flegal, Farrah N.
    Figel, Markus
    Garcia, Omar
    Gil, Octavia Monteiro
    Gregoire, Eric
    Guerrero-Carbajal, C.
    Guclu, Inci
    Hadjidekova, Valeria
    Hande, Prakash
    Kulka, Ulrike
    Lemon, Jennifer
    Lindholm, Carita
    Lista, Florigio
    Lumniczky, Katalin
    Martinez-Lopez, Wilner
    Maznyk, Nataliya
    Meschini, Roberta
    M'kacher, Radia
    Montoro, Alegria
    Moquet, Jayne
    Moreno, Mercedes
    Noditi, Mihaela
    Pajic, Jelena
    Radl, Analia
    Ricoul, Michelle
    Romm, Horst
    Roy, Laurence
    Sabatier, Laure
    Sebastia, Natividad
    Slabbert, Jacobus
    Sommer, Sylwester
    Oliveira, Monica Stuck
    Subramanian, Uma
    Suto, Yumiko
    Tran, Que
    Testa, Antonella
    Terzoudi, Georgia
    Vral, Anne
    Wilkins, Ruth
    Yanti, LusiYanti
    Zafiropoulos, Demetre
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    RENEB intercomparisons applying the conventional Dicentric Chromosome Assay (DCA)2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 20-29Article in journal (Refereed)
    Abstract [en]

    Purpose: Two quality controlled inter-laboratory exercises were organized within the EU project 'Realizing the European Network of Biodosimetry (RENEB)' to further optimize the dicentric chromosome assay (DCA) and to identify needs for training and harmonization activities within the RENEB network. Materials and methods: The general study design included blood shipment, sample processing, analysis of chromosome aberrations and radiation dose assessment. After manual scoring of dicentric chromosomes in different cell numbers dose estimations and corresponding 95% confidence intervals were submitted by the participants. Results: The shipment of blood samples to the partners in the European Community (EU) were performed successfully. Outside the EU unacceptable delays occurred. The results of the dose estimation demonstrate a very successful classification of the blood samples in medically relevant groups. In comparison to the 1st exercise the 2nd intercomparison showed an improvement in the accuracy of dose estimations especially for the high dose point. Conclusions: In case of a large-scale radiological incident, the pooling of ressources by networks can enhance the rapid classification of individuals in medically relevant treatment groups based on the DCA. The performance of the RENEB network as a whole has clearly benefited from harmonization processes and specific training activities for the network partners.

  • 122.
    Olofsson, Jonas K.
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Northwestern University Feinberg School of Medicine, USA; Swedish Collegium for Advanced Study, Sweden.
    Hurley, Robert S.
    Bowman, Nicholas E.
    Bao, Xiaojun
    Mesulam, M. -Marsel
    Gottfried, Jay A.
    A Designated Odor-Language Integration System in the Human Brain2014In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 34, no 45, p. 14864-14873Article in journal (Refereed)
    Abstract [en]

    Odors are surprisingly difficult to name, but the mechanism underlying this phenomenon is poorly understood. In experiments using event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI), we investigated the physiological basis of odor naming with a paradigm where olfactory and visual object cues were followed by target words that either matched or mismatched the cue. We hypothesized that word processing would not only be affected by its semantic congruency with the preceding cue, but would also depend on the cue modality (olfactory or visual). Performance was slower and less precise when linking a word to its corresponding odor than to its picture. The ERP index of semantic incongruity (N400), reflected in the comparison of nonmatching versus matching target words, was more constrained to posterior electrode sites and lasted longer on odor-cue (vs picture-cue) trials. In parallel, fMRI cross-adaptation in the right orbitofrontal cortex (OFC) and the left anterior temporal lobe (ATL) was observed in response to words when preceded by matching olfactory cues, but not by matching visual cues. Time-series plots demonstrated increased fMRI activity in OFC and ATL at the onset of the odor cue itself, followed by response habituation after processing of a matching (vs nonmatching) target word, suggesting that predictive perceptual representations in these regions are already established before delivery and deliberation of the target word. Together, our findings underscore the modality-specific anatomy and physiology of object identification in the human brain.

  • 123.
    Olsson, Gunilla
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Czene, Stefan
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Harms-Ringdahl, Mats
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Transient delay of radiation-induced apoptosis by phorbol acetate2016In: Radiation and Environmental Biophysics, ISSN 0301-634X, E-ISSN 1432-2099, Vol. 55, no 1, p. 95-102Article in journal (Refereed)
    Abstract [en]

    The mechanisms of interference of a model tumour promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) with radiation-induced apoptosis in human peripheral lymphocytes have been investigated. The cells were treated with TPA under various conditions and thereafter exposed to a single lethal dose of gamma radiation. Morphological and biochemical changes characteristic of apoptosis were followed up to 72 h of post-irradiation time. Acute exposure to low concentration of TPA resulted in delay in the onset of radiation-induced apoptosis (determined as morphological changes and rate of mitochondrial demise) by 24-48 h as compared to the irradiated, sham TPA-treated cells. The time course of this delay correlated well with confinement of the p53 protein to the cytoplasm and increase in bcl-2 levels at the nuclear periphery of irradiated cells. Our results indicate that confinement of p53 in the cytoplasm is one of the potential mechanisms by which TPA interferes with the process of radiation-induced apoptosis in human lymphocytes.

  • 124.
    Omar, Artur
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Silicon Diode Dose Response Correction in Small Photon Fields2010Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Silicon diodes compared to other types of dosimeters have several attractive properties, such as an excellent spatial resolution, a high sensitivity, and clinically practical to use. These properties make silicon diodes a preferred dosimeter for relative dosimetry for several types of measurements in small field dosimetry, e.g., stereotactic treatments and intensity modulated radiotherapy (IMRT). Silicon diodes are, however, limited by an energy dependent response variation in photon beams, resulting in that the diode readout per dose to the phantom medium varies with photon spectral changes, thereby introducing a significant uncertainty in the measured data. The traditional solution for the energy dependent over-response caused by low-energy photons is to use diodes with a shielding filter of high atomic number. These shielded diodes, however, show an incorrect readout for small fields due to electrons scattered from the shielding (Griessbach et al. 2005). In regions with degraded lateral electron equilibrium (LEE) shielded diodes over-respond due to an increased degree of LEE, as a consequence of the high density shielding (Lee et al. 2002).

    In this work a prototype software that corrects for the energy dependent response of a silicon diode is developed and validated for small field sizes. The developed software is based on the novel concept of Monte Carlo (MC) simulated fluence pencil beam kernels to calculate spectra (Eklund and Ahnesjö 2008), and the spectra based silicon diode response model proposed by Eklund and Ahnesjö (2009). The software was also extended to include correction of ionization chambers, for the energy dependent Spencer-Attix water/air stopping power ratio (sw,air). The calculated sw,air are shown to be in excellent agreement with published values to better than 0.1% for most values, the maximum deviation being 0.3%.

    Measured relative depth doses, relative profiles, and output factors in water, for small square field sizes, for 6 MV and 15 MV clinical photon beams are presented in this work. The results show that the unshielded Scanditronix-Wellhöfer EFD3G silicon diode response, corrected by the developed software, is in excellent agreement with reference ionization chamber measurements (corrected for change in sw,air), the maximum deviation being 0.4%.

    Measurements with two types of shielded diodes, namely Scanditronix-Wellhöfer PFD silicon diodes (FP1990 and FP2730), are also included in this work. The shielded diodes are shown to have an over-response as large as 2-3.5% for field sizes smaller than 5 cm x 5 cm. The presented results also suggest a difference in accuracy as large as 0.5-1% between the two types of shielded diodes, where the spectral composition at the measurement position dictates which type of diode is more accurate.

    The fast correction of silicon diodes provided by the developed software is more accurate than shielded diodes for small field sizes, and can in radiotherapeutic clinical practice increase the dosimetric accuracy of silicon diodes.

  • 125. 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.

  • 126.
    Papenberg, Göran
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Ferencz, Beata
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Mangialasche, Francesca
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Mecocci, Patrizia
    Cecchetti, Roberta
    Kalpouzos, Gregoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Physical activity and inflammation: effects on gray-matter volume and cognitive decline in aging2016In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 37, no 10, p. 3462-3473Article in journal (Refereed)
    Abstract [en]

    Physical activity has been positively associated with gray-matter integrity. In contrast, pro-inflammatory cytokines seem to have negative effects on the aging brain and have been related to dementia. It was investigated whether an inactive lifestyle and high levels of inflammation resulted in smaller gray-matter volumes and predicted cognitive decline across 6 years in a population-based study of older adults (n=414). Self-reported physical activity (fitness-enhancing, health-enhancing, inadequate) was linked to gray-matter volume, such that individuals with inadequate physical activity had the least gray matter. There were no overall associations between different pro-and anti-inflammatory markers (IL-1, IL-6, IL-10, IL-12p40, IL-12p70, G-CSF, and TNF-) and gray-matter integrity. However, persons with inadequate activity and high levels of the pro-inflammatory marker IL-12p40 had smaller volumes of lateral prefrontal cortex and hippocampus and declined more on the Mini-Mental State Examination test over 6 years compared with physically inactive individuals with low levels of IL-12p40 and to more physically active persons, irrespective of their levels of IL-12p40. These patterns of data suggested that inflammation was particularly detrimental in inactive older adults and may exacerbate the negative effects of physical inactivity on brain and cognition in old age. Hum Brain Mapp 37:3462-3473, 2016.

  • 127.
    Peira, Nathalie
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Perception and psychophysics. Uppsala University, Sweden.
    Ziaei, Maryam
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm University, Faculty of Social Sciences, Department of Psychology, Cognitive psychology.
    Age differences in brain systems supporting transient and sustained processes involved in prospective memory and working memory2016In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 125, p. 745-755Article in journal (Refereed)
    Abstract [en]

    In prospective memory (PM), an intention to act in response to an external event is formed, retained, and at a later stage, when the event occurs, the relevant action is performed. PM typically shows a decline in late adulthood, which might affect functions of daily living. The neural correlates of this decline are not well understood. Here, 15 young (6 female; age range = 23-30 years) and 16 older adults (5 female; age range = 64-74 years) were scanned with fMRI to examine age-related differences in brain activation associated with event-based PM using a task that facilitated the separation of transient and sustained components of PM. We show that older adults had reduced performance in conditions with high demands on prospective and working memory, while no age-difference was observed in low-demanding tasks. Across age groups, PM task performance activated separate sets of brain regions for transient and sustained responses. Age-differences in transient activation were found in fronto-striatal and MTL regions, with young adults showing more activation than older adults. Increased activation in young, compared to older adults, was also found for sustained PM activation in the IFG. These results provide new evidence that PM relies on dissociable transient and sustained cognitive processes, and that age-related deficits in PM can be explained by an inability to recruit PM-related brain networks in old age.

  • 128.
    Persson, Jonas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Kalpouzos, Gregoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Ryberg, Mats
    Nyberg, Lars
    Preserved Hippocampus Activation in Normal Aging as Revealed by fMRI2011In: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 21, no 7, p. 753-766Article in journal (Refereed)
    Abstract [en]

    The hippocampus is deteriorated in various pathologies such as Alzheimer's disease (AD) and such deterioration has been linked to memory impairment. By contrast, the structural and functional effects of normal aging on the hippocampus is a matter of debate, with some findings suggesting deterioration and others providing evidence of preservation. This constitutes a crucial question since many investigations on AD are based on the assumption that the deterioration of the hippocampus is the breaking point between normal and pathological aging. A growing number of fMRI studies specifically aimed at investigating hippocampal engagement in various cognitive tasks, notably memory tasks, but the results have been inconclusive. Here, we optimized the episodic face-name paired-associates task in order to test the functioning of the hippocampus in normal aging. Critically, we found no difference in the activation of the hippocampus between the young and a group of older participants. Analysis of individual patterns of activation substantiated this impression. Collectively, these findings provide evidence of preserved hippocampal functioning in normal aging.

  • 129.
    Persson, Jonas
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Larsson, Anne
    Reuter-Lorenz, Patricia A.
    Imaging Fatigue of Interference Control Reveals the Neural Basis of Executive Resource Depletion2013In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 25, no 3, p. 338-351Article in journal (Refereed)
    Abstract [en]

    Executive control coordinates, prioritizes, and selects task-relevant representations under conditions of conflict. Behavioral evidence has documented that executive resources are separable, finite, and can be temporarily depleted; however, the neural basis for such resource limits are largely unknown. Here, we investigate the neural correlates underlying the fatigue or depletion of interference control, an executive process hypothesized to mediate competition among competing memory representations. Using a pre/post continuous acquisition fMRI design, we demonstrate that, compared with a nondepletion control group, the depletion group showed a fatigue-induced performance deficit that was specific to interference control and accompanied by a left-to-right shift in the network of active regions. Specifically, we observed decreased BOLD signal in the left inferior frontal gyrus (IFG), striatum, and the cerebellum, along with a corresponding increase in right hemisphere regions including the IFG, insular, and temporal cortex. Depletion-related changes in activation magnitude correlated with behavioral changes, suggesting that decreased recruitment of task-relevant regions, including left IFG, contributes to impaired interference control. These results provide new evidence about the brain dynamics of "process-specific" fatigue and suggest that depletion may pose a significant limitation on the cognitive and neural resources available for executive control.

  • 130.
    Persson, Jonas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Pudas, Sara
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Lind, Johanna
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Kauppi, Karolina
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Longitudinal structure – function correlates in elderly reveal MTL dysfunction with cognitive decline2012In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 22, no 10, p. 2297-2304Article in journal (Refereed)
    Abstract [en]

    By integrating behavioral measures and imaging data, previous investigations have explored the relationship between biological markers of aging and cognitive functions. Evidence from functional and structural neuroimaging has revealed that hippocampal volume and activation patterns in the medial temporal lobe (MTL) may predict cognitive performance in old age. Most past demonstrations of age-related differences in brain structure–function were based on cross-sectional comparisons. Here, the relationship between 6-year intraindividual change in functional magnetic resonance imaging (fMRI) signal and change in memory performance over 2 decades was examined. Correlations between intraindividual change in fMRI signal during episodic encoding and change in memory performance measured outside of scanning were used as an estimate for relating brain–behavior changes. The results revealed a positive relationship between activation change in the hippocampus (HC) and change in memory performance, reflecting reduced hippocampal activation in participants with declining performance. Using a similar analytic approach as for the functional data, we found that individuals with declining performance had reduced HC volume compared with individuals with intact performance. These observations provide a strong link between cognitive change in older adults and MTL structure and function and thus provide insights into brain correlates of individual variability in aging trajectories.

  • 131.
    Persson, Linda M.
    Stockholm University.
    Cell survival at low and high ionisation densities investigated with a new model2002Doctoral thesis, comprehensive summary (Other academic)
  • 132.
    Persson, Ninni
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm Brain Institute, Sweden; Wayne State University, USA.
    Ghisletta, P.
    Dahle, C. L.
    Bender, A. R.
    Yang, Y.
    Yuan, P.
    Daugherty, A. M.
    Raz, N.
    Regional brain shrinkage over two years: Individual differences and effects of pro-inflammatory genetic polymorphisms2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 103, p. 334-348Article in journal (Refereed)
    Abstract [en]

    We examined regional changes in brain volume in healthy adults (N = 167, age 19–79 years at baseline; N = 90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the Hc, CbH, In, OF, and PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants modified shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1β (IL-1β C-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFR C677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) ε4 allele were noted. These results replicate the pattern of brain shrinkage observed in previous studies, with a notable exception of the LPFC, thus casting doubt on the unique importance of prefrontal cortex in aging. Larger baseline volumes of CbH and In were associated with increased shrinkage, in conflict with the brain reserve hypothesis. Contrary to previous reports, we observed no significant linear effects of age and hypertension on regional brain shrinkage. Our findings warrant further investigation of the effects of neuroinflammation on structural brain change throughout the lifespan.

  • 133.
    Persson, Ninni
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm Brain Institute, Sweden; Weill Cornell Medical College, USA.
    Wu, Jianlin
    Zhang, Qing
    Liu, Ting
    Shen, Jing
    Bao, Ruyi
    Ni, Mingfei
    Liu, Tian
    Wang, Yi
    Spincemaille, Pascal
    Age and sex related differences in subcortical brain iron concentrations among healthy adults2015In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 122, p. 385-398Article in journal (Refereed)
    Abstract [en]

    Age and sex can influence brain iron levels. We studied the influence of these variables on deep gray matter magnetic susceptibilities. In 183 healthy volunteers (44.7 ± 14.2 years, range 20–69, ♀ 49%), in vivo quantitative susceptibility mapping (QSM) at 1.5 T was performed to estimate brain iron accumulation in the following regions of interest (ROIs): caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), thalamus (Th), pulvinar (Pul), red nucleus (Rn), substantia nigra (Sn) and the cerebellar dentate nuclei (Dn). We gauged the influence of age and sex on magnetic susceptibility by specifying a series of structural equation models. The distributions of susceptibility varied in degree across the structures, conforming to histologic findings (Hallgren and Sourander, 1958), with the highest degree of susceptibility in the Gp and the lowest in the Th. Iron increase correlated across several ROIs, which may reflect an underlying age-related process. Advanced age was associated with a particularly strong linear rise of susceptibility in the striatum. Nonlinear age trends were found in the Rn, where they were the most pronounced, followed by the Pul and Sn, while minimal nonlinear trends were observed for the Pt, Th, and Dn. Moreover, sex related variations were observed, so that women showed lower levels of susceptibility in the Sn after accounting for age. Regional susceptibility of the Pul increased linearly with age in men but exhibited a nonlinear association with age in women with a leveling off starting from midlife. Women expected to be post menopause (+ 51 years) showed lower total magnetic susceptibility in the subcortical gray matter. The current report not only is consistent with previous reports of age related variations of brain iron, but also adds to the current knowledge by reporting age-related changes in less studied, smaller subcortical nuclei. This is the first in-vivo report to show lower total subcortical brain iron levels selectively in women from midlife, compared to men and younger women. These results encourage further assessment of sex differences in brain iron. We anticipate that age and sex are important co-factors to take into account when establishing a baseline level for differentiating pathologic neurodegeneration from healthy aging. The variations in regional susceptibility reported herein should be evaluated further using a longitudinal study design to determine within-person changes in aging.

  • 134.
    Qiu, C
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Cotch, M F
    Sigurdsson, S
    Jonsson, P V
    Jonsdottir, M K
    Sveinbjornsdottir, S
    Eiriksdottir, G
    Klein, R
    Harris, T B
    van Buchem, M A
    Gudnason, V
    Launer, L J
    Cerebral microbleeds, retinopathy, and dementia: the AGES-Reykjavik Study2010In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 75, no 24, p. 2221-8Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine whether microvascular damage, indicated by cerebral microbleeds (CMBs) and retinal microvascular signs, is associated with cognitive function and dementia in older persons.

    METHODS: This is a cross-sectional study of 3,906 participants (mean age 76 years; 58% women) in the AGES-Reykjavik Study (2002-2006). We assessed CMBs on MRI and retinal microvascular signs on digital retinal images. Composite Z scores of memory, processing speed, and executive function were derived from a battery of neurocognitive tests. Dementia and subtypes were diagnosed following international criteria. Regression models were used to relate cognitive Z scores and dementia to CMBs and retinal microvascular signs, adjusting for demographics, cardiovascular factors, and brain ischemic lesions.

    RESULTS: People with multiple (≥ 2) CMBs had lower Z scores on tests of processing speed (β-coefficient -0.16; 95% confidence interval -0.26 to -0.05) and executive function (-0.14; -0.24 to -0.04); results were strongest for having multiple CMBs located in the deep hemispheric or infratentorial areas. The odds ratio of vascular dementia was 2.32 (95% confidence interval 1.02 to 5.25) for multiple CMBs and 1.95 (1.04 to 3.62) for retinopathy. Having both CMBs and retinopathy, compared to having neither, was significantly associated with markedly slower processing speed (-0.25; -0.37 to -0.12), poorer executive function (-0.19; -0.31 to -0.07), and an increased odds ratio of vascular dementia (3.10; 1.11 to 8.62).

    CONCLUSION: Having multiple CMBs or concomitant CMBs and retinopathy is associated with a profile of vascular cognitive impairment. These findings suggest that microvascular damage, as indicated by CMBs and retinopathy lesions, has functional consequences in older men and women living in the community.

  • 135.
    Rieckmann, Anna
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Karlsson, Sari
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Caudate Dopamine D1 Receptor Density Is Associated with Individual Differences in Frontoparietal Connectivity during Working Memory2011In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 31, no 40, p. 14284-14290Article in journal (Refereed)
    Abstract [en]

    We assess the relationship of age-related losses in striatal D1 receptor densities to age-related reductions in functional connectivity between spatially distinct cortical regions in healthy human participants. Previous neuroimaging studies have reported age-related differences in functional connectivity of the frontoparietal working memory network and the default mode network during task performance. We used functional magnetic resonance imaging and seed-based connectivity (right dorsolateral and medial prefrontal cortex) to extend these findings: Anterior-posterior connectivity of both these functional networks was reduced in older (65-75 years, n = 18) compared with younger (20-30 years, n = 19) adults, whereas bilateral connectivity in prefrontal cortex was increased in older adults. Positron emission tomography with the D1 receptor ligand [(11)C]SCH23390 was used to assess caudate D1 receptor density in the same sample. Older adults showed significantly reduced caudate D1 receptor density compared to the younger adults. Of key interest, partial correlations showed that individual differences in caudate D1 receptor density were positively associated with individual differences in dorsolateral prefrontal connectivity to right parietal cortex (BA40) and negatively with medial prefrontal connectivity to right parietal cortex (BA40 and postcentral gyrus), after controlling for age. We found no correlation of caudate D1 receptor density with anterior-posterior coupling within the default mode network or with bilateral frontal connectivity. These results are consistent with animal work that has identified a role for caudate D1 receptors in mediating information transfer between prefrontal areas and parietal cortex.

  • 136.
    Rieckmann, Anna
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Karlsson, Sari
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Karlsson, Per
    Brehmer, Yvonne
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Farde, Lars
    Nyberg, Lars
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Dopamine D1 Receptor Associations within and between Dopaminergic Pathways in Younger and Elderly Adults: Links to Cognitive Performance2011In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 21, no 9, p. 2023-2032Article in journal (Refereed)
    Abstract [en]

    Age-related dopamine (DA) losses have been extensively demonstrated for the D2 receptor subtype. Comparatively little is known about adult age changes regarding D1 receptors. In this study, we demonstrate marked age-related D1 receptor losses in striatal, limbic, and cortical areas using positron emission tomography and the radioligand [11C]SCH23390 in humans. Interregional correlations of binding potential (BP) values were high for areas within DA pathways in younger and elderly adults alike. Furthermore, interregional correlations in D1 BP between DA pathways were uniformly high in younger adults, indicating that D1 receptor densities in striatal, limbic, and cortical areas are not regulated independently, despite dopaminergic innervation from different midbrain areas. For elderly adults, between-pathway correlations of D1 receptor densities were preserved only between mesolimbic and mesocortical areas, whereas striatal BPs were weakly related to those in limbic and neocortical regions. Importantly, weak between-pathway correlations in elderly adults were found only for the slower half of the sample when BP was estimated during a cognitive interference task. These results suggest that D1 receptor densities in different pathways are not regulated independently in younger adults, but segregate in older age, and that this segregation of D1 receptor systems may be related to age-related cognitive slowing.

  • 137. 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.

  • 138. Roland, Teboh
    et al.
    Tryggestad, Erik
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Department of Physics.
    Hales, Russell
    Papanikolaou, Nikos
    The radiobiological P+ index for pretreatment plan assessment with emphasis on four-dimensional radiotherapy modalities2012In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 39, no 10, p. 6420-6430Article in journal (Refereed)
    Abstract [en]

    Purpose: Radiation treatment modalities will continue to emerge that promise better clinical outcomes albeit technologically challenging to implement. An important question facing the radiotherapy community then is the need to justify the added technological effort for the clinical return. Mobile tumor radiotherapy is a typical example, where 4D tumor tracking radiotherapy (4DTRT) has been proposed over the simpler conventional modality for better results. The modality choice per patient can depend on a wide variety of factors. In this work, we studied the complication-free tumor control probability (P+) index, which combines the physical complexity of the treatment plan with the radiobiological characteristics of the clinical case at hand and therefore found to be useful in evaluating different treatment techniques and estimating the expected clinical effectiveness of different radiation modalities. Methods: 4DCT volumes of 18 previously treated lung cancer patients with tumor motion and size ranging from 2 mm to 15 mm and from 4 cc to 462 cc, respectively, were used. For each patient, 4D treatment plans were generated to extract the 4D dose distributions, which were subsequently used with clinically derived radiobiological parameters to compute the P+ index per modality. Results: The authors observed, on average, a statistically significant increase in P+ of 3.4% +/- 3.8% (p < 0.003) in favor of 4DTRT. There was high variability among the patients with a < 0.5% up to 13.4% improvement in P+. Conclusions: The observed variability in the improvement of the clinical effectiveness suggests that the relative benefit of tracking should be evaluated on a per patient basis. Most importantly, this variability could be effectively captured in the computed P+. The index can thus be useful to discriminate and hence point out the need for a complex modality like 4DTRT over another. Besides tumor mobility, a wide range of other factors, e.g., size, location, fractionation, etc., can affect the relative benefits. Application of the P+ objective is a simple and effective way to combine these factors in the evaluation of a treatment plan.

  • 139. Romm, Horst
    et al.
    Ainsbury, Elizabeth A.
    Francesc Barquinero, Joan
    Barrios, Leonardo
    Beinke, Christina
    Cucu, Alexandra
    Moreno Domene, Mercedes
    Filippi, Silvia
    Gil, Octavia Monteiro
    Gregoire, Eric
    Hadjidekova, Valeria
    Hatzi, Vasia
    Lindholm, Carita
    M'kacher, Radhia
    Montoro, Alegria
    Moquet, Jayne
    Noditi, Mihaela
    Oestreicher, Ursula
    Palitti, Fabrizio
    Pantelias, Gabriel
    Jesus Prieto, Maria
    Popescu, Irina
    Rothkamm, Kai
    Sebastia, Natividad
    Sommer, Sylwester
    Terzoudi, Georgia
    Testa, Antonella
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Jan Kochanowski University, Poland.
    Web based scoring is useful for validation and harmonisation of scoring criteria within RENEB2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 110-117Article in journal (Refereed)
    Abstract [en]

    Purpose: To establish a training data set of digital images and to investigate the scoring criteria and dose assessment of the dicentric assay within the European network of biodosimetry (RENEB), a web based scoring inter-comparison was undertaken by 17 RENEB partners. Materials and methods: Two sets of 50 high resolution images were uploaded onto the RENEB web site. One set included metaphases after a moderate exposure (1.3 Gy) and the other set consisted of metaphases after a high dose exposure (3.5 Gy). The laboratories used their own calibration curves for estimating doses based on observed aberration frequencies. Results: The dose estimations and 95% confidence limits were compared to the actual doses and the corresponding z-values were satisfactory for the majority; only the dose estimations from two laboratories were too low or too high. The coefficients of variation were 17.6% for the moderate and 11.2% for the high dose. Metaphases with controversial results could be identified for training purposes. Conclusions: Overall, the web based scoring of the two galleries by the 17 laboratories produced very good results. Application of web based scoring for the dicentric assay may therefore be a relevant strategy for an operational biodosimetry assistance network.

  • 140.
    Rutkowska, Eva
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Dose-Volume Histogram Analysis of Stereotactic Body Radiation Therapy of Liver Tumours2006Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Background: Stereotactic body radiation therapy (SBRT) is a relatively new method which has been employed e.g. in the treatment of liver tumours. Little dosimetric data has been published for SBRT in the liver. The aim of this retrospective study was to quantify the dosimetric parameters that influence the toxicity of the healthy liver, and the effect on the tumour, for SBRT to liver tumours in patients treated at Karolinska University Hospital. A comparison was made to relating published studies.

    Patients and Methods: The patient group to be studied were treated at Karolinska University Hospital for liver metastases with SBRT between July 1993 and October 2004. There were 64 patients treated with 71 treatment plans for 81 tumours. Differential dose volume histograms were collected for the clinical target volume (CTV), the planning target volume (PTV) and the liver excluding the CTV, from all dose plans. Since different fractionation schedules were used, the doses were normalised using the linear quadratic model, to be comparable. The doses to the uninvolved liver were evaluated with the mean liver dose, the Lyman-Kutcher-Burman (LKB) effective volume normal tissue complication probability (NTCP) model as well as the critical volume NTCP-model. A comparison was made to the studies of Dawson et al (2002) and Schefter et al (2005). The doses to the CTV were evaluated using the equivalent uniform dose tumour control probability (TCP) model, and related to target size and date of treatment.

    Results: When the mean doses to the uninvolved liver (the liver volume without tumour tissue) were compared to Dawson and Ten Haken’s results (2005), 20 treatments out of 71 were predicted to give a risk of radiation induced liver disease (RILD) higher than 50%. The effective volume calculations predicted that 18 treatments gave a risk of RILD higher than 50%, when compared to the results of Dawson et al (2002). According to the critical volume model and the parameter values of Schefter et al (2005), our data predict that 10 of the treatments gave a risk of liver function failure, to an unspecified risk level. Treatments of large tumours resulted in higher doses to the liver. The doses to the CTV showed that the maximum prescribed dose decreased with increasing CTV.

    Discussion and Conclusions: An evaluation of clinical data is necessary to make a full analysis of the treatments of this study. Such an analysis is planned for the future.

  • 141. Salomaa, Sisko
    et al.
    Prise, Kevin M.
    Atkinson, Michael J.
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Stockholm Univ, Ctr Radiat Protect Res..
    Auvinen, Anssi
    Grosche, Bernd
    Sabatier, Laure
    Jourdain, Jean-Rene
    Salminen, Eeva
    Baatout, Sarah
    Kulka, Ulrike
    Rabus, Hans
    Blanchardon, Eric
    Averbeck, Dietrich
    Weiss, Wolfgang
    State of the art in research into the risk of low dose radiation exposure-findings of the fourth MELODI workshop2013In: Journal of Radiological Protection, ISSN 0952-4746, E-ISSN 1361-6498, Vol. 33, no 3, p. 589-603Article in journal (Refereed)
    Abstract [en]

    The fourth workshop of the Multidisciplinary European Low Dose Initiative (MELODI) was organised by STUK-Radiation and Nuclear Safety Authority of Finland. It took place from 12 to 14 September 2012 in Helsinki, Finland. The meeting was attended by 179 scientists and professionals engaged in radiation research and radiation protection. We summarise the major scientific findings of the workshop and the recommendations for updating the MELODI Strategic Research Agenda and Road Map for future low dose research activities.

  • 142.
    Segerdahl, Tony
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    MRI Safety, Test Methods and Construction of a Database2007Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Magnetic Resonance Imaging, MRI, is a diagnostic tool in progress which has been available at major hospitals since the mid eighties. Today almost all hospitals world wide may depict the human body with their own MRI scanner. MRI is dependent on a uniform magnetic field inside the scanner tunnel and Radio frequent (RF) waves used for excitation of the magnetic dipole moments in the body. These properties along with the magnetic field surrounding the scanner are associated with dangerous effects - when interacting with medical implants made of metals. These dangerous effects are twisting forces or torques, heating and translational forces respectively. A database containing information about known implants behaviour regarding these effects among with earlier documentation and information concerning MRI patient safety at Karolinska hospital, Huddinge was constructed.

    Also a phantom used for heating effect measurements was constructed and heating effect measurements were performed at a SPC4129 locking titanium Peritoneal Dialysis (PD) catheter adapter and a Deep Brain Stimulator (DBS) in order to test the phantom and confirm the theory about RF induced heating on medical implants. Evidence for heating effects caused by the implants was found.

    A torque measurement apparatus was constructed and measurements were performed. All measurements where performed in order to investigate the functionality of the apparatus and also the theory behind dangerous magnetically induced torques (twisting movements). Substantial torque were measured on the ferromagnetic device used for the test.

    The heating phantom and torque measurement apparatus is slightly modified models of those proposed by ASTM (American Society for Testing and Materials).

  • 143.
    Seubert, Janina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Pennsylvania, USA.
    Ohla, Kathrin
    Yokomukai, Yoshiko
    Kellermann, Thilo
    Lundström, Johan N.
    Superadditive Opercular Activation to Food Flavor is Mediated by Enhanced Temporal and Limbic Coupling2015In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 36, no 5, p. 1662-1676Article in journal (Refereed)
    Abstract [en]

    Food perception is characterized by a transition from initially separate sensations of the olfactory and gustatory properties of the object toward their combined sensory experience during consumption. The holistic flavor experience, which occurs as the smell and taste merge, extends beyond the mere addition of the two chemosensory modalities, being usually perceived as more object-like, intense and rewarding. To explore the cortical mechanisms which give rise to olfactory-gustatory binding during natural food consumption, brain activation during consumption of a pleasant familiar beverage was contrasted with presentation of its taste and orthonasal smell alone. Convergent activation to all presentation modes was observed in executive and chemosensory association areas. Flavor, but not orthonasal smell or taste alone, stimulated the frontal operculum, supporting previous accounts of its central role in the formation of the flavor percept. A functional dissociation was observed in the insula: the anterior portion was characterized by sensory convergence, while mid-dorsal sections activated exclusively to the combined flavor stimulus. psycho-physiological interaction analyses demonstrated increased neural coupling between the frontal operculum and the anterior insula during flavor presentation. Connectivity was also increased with the lateral entorhinal cortex, a relay to memory networks and central node for contextual modulation of olfactory processing. These findings suggest a central role of the insular cortex in the transition from mere detection of chemosensory convergence to a superadditive flavor representation. The increased connections between the frontal operculum and medial temporal memory structures during combined olfactory-gustatory stimulation point to a potential mechanism underlying the acquisition and modification of flavor preferences. Hum Brain Mapp 36:1662-1676, 2015.

  • 144. Somaiah, Navita
    et al.
    Yarnold, John
    Lagerqvist, Anne
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Rothkamm, Kai
    Helleday, Thomas
    Homologous recombination mediates cellular resistance and fraction size sensitivity to radiation therapy2013In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 108, no 1, p. 155-161Article in journal (Refereed)
    Abstract [en]

    Purpose: Cellular sensitivity to radiotherapy total dose and fraction size is strongly influenced by DNA double strand break (DSB) repair. Here, we investigate response to radiotherapy fraction size using CHO cell lines deficient in specific DNA repair pathways in response to radiation induced DNA double strand breaks (DSB). Experimental design: We irradiated CHO cell lines, AA8 (WT), irs1SF (XRCO-), V3-3 (DNA-PKcs-) and EM9 (XRCC1-) with 16 Gy in 1 Gy daily fractions over 3 weeks or 16 Gy in 4 Gy daily fractions over 4 days, and studied clonogenic survival, DNA DSB repair kinetics (RAD51 and 53BP1 foci staining) and cell cycle profiles (flow cytometry). Results: In response to fractionated radiotherapy, wild-type and DNA repair defective cells accumulated in late S/G2 phase. In cells proficient in homologous recombination (HR), accumulation in S/G2 resulted in reduced sensitivity to fraction size and increased cellular resistance (clonogenic survival). Sensitivity to fraction size was also lost in NHEJ-defective V3-3 cells, which likely rely on functional HR. By contrast, HR-defective irs1SF cells, with functional NHEJ, remained equally sensitive to fractionation throughout the 3-week treatment. Conclusions: The high fidelity of HR, which is independent of induced DNA damage level, is postulated to explain the low fractionation sensitivity and cellular resistance of cells in S/G2 phase. In conclusion, our results suggest that HR mediates resistance to fractionated radiotherapy, an observation that may help future efforts to improve radiotherapy outcome.

  • 145. Spulber, Gabriela
    et al.
    Niskanen, Eini
    Macdonald, Stuart
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Padilla, Daniel Ferreira
    Julkunen, Valtteri
    Hallikainen, Merja
    Vanninen, Ritva
    Wahlund, Lars-Olof
    Soininen, Hilkka
    Evolution of global and local grey matter atrophy on serial MRI scans during the progression from MCI to AD2012In: Current Alzheimer Research, ISSN 1567-2050, E-ISSN 1875-5828, Vol. 9, no 4, p. 516-524Article in journal (Refereed)
    Abstract [en]

    Mild cognitive impairment (MCI) often represents a prodromal form of dementia, conferring a significantly higher risk of converting to probable Alzheimer's disease (AD). The aim of this study is to characterise the differences of grey matter (GM) distribution and dynamics between progressive and stable MCI subjects during a 2 year period preceding the conversion to AD. We included 48 stable MCI and 12 progressive MCI cases based on the availability of 3 serial scans acquired with approximately 1 year scan interval. For the progressive MCI group, the third scan was acquired at the time of the clinical diagnosis of AD, while the first two scans were acquired approximately 2 and 1 years earlier. For the stable MCI group, the three scans were acquired at approximately 1 year intervals during a period free from significant cognitive decline. We used longitudinal voxel-based morphometry (VBM) for mapping the progression of GM loss over time. For the progressive MCI group, the cross-sectional analysis revealed areas of lower GM volumes in the parahippocampal gyrus, precuneus and posterior cingulate 12 months before the AD diagnosis. For the longitudinal VBM analysis the progressive MCI group revealed increased GM loss in cortical regions belonging to the temporal neocortex, parahippocampal cortex, and cingulate gyrus. The frontal lobe, insula and the cerebellum were also affected. This accelerated atrophy may offer new insights into the understanding of neurodegenerative pathology and the clinical relevance of these changes remains to be verified by subsequent studies.

  • 146. Su, F-C
    et al.
    Shi, C
    Mavroidis, Panayiotis
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Goytia, V
    Crownover, R
    Rassiah-Szegedi, P
    Papanikolaou, N
    Assessing four-dimensional radiotherapy planning and respiratory motion-induced dose difference based on biologically effective uniform dose.2009In: Technology in Cancer Research & Treatment (Trykt), ISSN 1533-0346, E-ISSN 1533-0338, Vol. 8, no 3, p. 187-200Article in journal (Refereed)
    Abstract [en]

    Four-dimensional (4D) radiotherapy is considered as a feasible and ideal solution to accommodate intra-fractional respiratory motion during conformal radiation therapy. With explicit inclusion of the temporal changes in anatomy during the imaging, planning, and delivery of radiotherapy, 4D treatment planning in principle provides better dose conformity. However, the clinical benefits of developing 4D treatment plans in terms of tumor control rate and normal tissue complication probability as compared to other treatment plans based on CT images of a fixed respiratory phase remains mostly unproven. The aim of our study is to comprehensively evaluate 4D treatment planning for nine lung tumor cases with both physical and biological measures using biologically effective uniform dose (D =) together with complication-free tumor control probability, P+. Based on the examined lung cancer patients and PTV margin applied, we found similar but not identical curves of DVH, and slightly different mean doses in tumor (up to 1.5%) and normal tissue in all cases when comparing 4D, P0%, and P50% plans. When it comes to biological evaluations, we did not observe definitively PTV size dependence in P+ among these nine lung cancer patients with various sizes of PTV. Moreover, it is not necessary that 4D plans would have better target coverage or higher P+ as compared to a fixed phase IMRT plan. However, on the contrary to significant deviations in P+ (up to 14.7%) observed if delivering the IMRT plan made at end-inhalation incorrectly at end-exhalation phase, we estimated the overall P+, PB, and PI for 4D composite plans that have accounted for intra-fractional respiratory motion.

  • 147.
    Svanholm, Ulrika
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Evaluation of measurements of pulsating flow under controlled conditions using phase contrast MRI2006Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The accuracy and precision of measurements of pulsating flow obtained with phase contrast magnetic resonance imaging (PC MRI) was studied. Measurements were carried out using known flow rates through a phantom connected to a pump that created pulsation in the flow. Repeated measurements were made in both the negative and positive encoding direction, using both breath-hold and non breath hold sequences. The obtained data was analyzed using code written in MATLAB and also using the FLOW software that is offered by the manufacturer of the MRI system.

    A range of different flow velocities was scanned, and results show that the overall accuracy of the measurements is relatively good, with an average error of between 1.2% to 5.7% using the clinically employed flow calculation software. There is however indication of a systematic phase offset in the data that influences the measurements. The effect of the offset on the results depends on the direction of flow and the sequence used. The results also show the importance of properly selecting the area over which the flow rate is calculated.

  • 148. Taleei, Reza
    et al.
    Hultqvist, Martha
    Stockholm University, Faculty of Science, Department of Physics. Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Gudowska, Irena
    Stockholm University, Faculty of Science, Department of Physics. Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Nikjoo, Hooshang
    A Monte Carlo evaluation of carbon and lithium ions dose distributions in water2012In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 88, no 1-2, p. 189-194Article in journal (Refereed)
    Abstract [en]

    Purpose: To compare dose distributions on the central- and off-axis for C-12 and Li-7 ion beams simulated by the codes SHIELD-HIT (Heavy Ion Transport) and FLUKA (FLUKtuierende KAskade), and compare with experimental data for 300 MeV/u C-12 and 185 MeV/u Li-7 ion beams.

    Materials and methods: The general purpose Monte Carlo codes, SHIELD-HIT10 and FLUKA 2008.3d. 1 were used for the ion dose distribution calculations. SHIELD-HIT transports hadrons and atomic nuclei of arbitrary charge and mass number in an energy range from 1 keV/u up to 1 GeV/u. Similarly, FLUKA transports charged hadrons in an energy range from 100 keV up to 20 TeV. Neutrons are transported down to thermal energies in both codes. Inelastic nuclear interactions are modelled in SHIELD-HIT by the Many Stage Dynamical Model (MSDM), whereas in FLUKA the Pre-Equilibrium Approach to Nuclear Thermalisation (PEANUT) package which includes a Generalized Intra-Nuclear Cascade model was used.

    Results: The dose distributions in water irradiated with 300 MeV/u C-12 and 185 MeV/u Li-7 ion beams were simulated with the two codes. Studies were performed of the energy deposition both on the central axis and at lateral distances up to 10 cm off-axis. The dose distributions calculated by SHIELD-HIT and FLUKA were compared with published experimental data. The dose mean lineal energy (y) over bar (D), frequency mean lineal energy (y) over bar (F), dose mean specific energy (z) over bar (D), and frequency mean specific energy (z) over bar (F) were calculated with the ion track-structure code PITS99 (Positive Ion Track Structure 99), coupled with the electron code KURBUC for the primary and secondary ions average energies at 1 mm before the Bragg peak.

    Conclusion: The Monte Carlo codes show good agreement with experimental results for off-axis dose distributions. The disagreements in the Bragg peak region for the central-axis dose distributions imply that further improvements especially in the nuclear interaction models are required to increase the accuracy of the codes.

  • 149.
    Tamras, Dina
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Verification of dose limitation of the general public and determination of lead equivalence of x-ray rooms at Karolinska University Hospital Huddinge2006Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    A variety of radiation sources exist at the Department of Radiology and the Department of Nuclear Medicine at Karolinska University Hospital Huddinge. Radiation sources can also be found in areas outside of these departments due to the wide use of mobile xray machines and fluoroscopic c-arm equipment and also due to the movement of patients that have received diagnostic or therapeutic doses of radionuclides.

    In a proposal for a new legislation from the Swedish Radiation Protection Authority (SSI), which was later issued as legislation SSI FS 2005:6, the effective doses of the general public from a practice using ionising radiation need to be kept below stated limit of 0.1 mSv/year. This project was performed to verify the dose limit for individuals of the general public in the above mentioned practices.

    Long-term measurements with TL-dosimeters were utilised to carry out the environmental monitoring of the areas throughout the Departments of Radiology and Nuclear Medicine. To assess the contribution of ionising radiation from rooms housing mobile fluoroscopic c-arm equipment to surrounding areas, a tissue equivalent phantom of size (30×30×20 cm3) was employed to simulate a patient and the scattered radiation was monitored by using area monitors, such as portable proportional counters. The annual effective doses were calculated in terms of personal dose equivalent as well as ambient dose equivalent monitored using TL-dosimeters and area monitors, respectively. The stated limit of 0.1 mSv/year to the general public was verified by risk analysis.

    An attempt to create a method for determining the amount of radiation shielding in terms of lead equivalence in walls, doors, protective glasses of manoeuvre rooms and cupboards of diagnostic x-ray labs was also performed using a radiation point source of 99mTc and a NaI scintillation detector. Depending on the accuracy in the measurements the amount of lead deviated slightly from the expected 2 mm value based on the former legislation SSI FS 1991:1.

  • 150. Terzoudi, Georgia I.
    et al.
    Pantelias, Gabriel
    Darroudi, Firouz
    Barszczewska, Katarzyna
    Buraczewska, Iwona
    Depuydt, Julie
    Georgieva, Dimka
    Hadjidekova, Valeria
    Hatzi, Vasiliki I.
    Karachristou, Ioanna
    Karakosta, Maria
    Meschini, Roberta
    M'Kacher, Radhia
    Montoro, Alegria
    Palitti, Fabrizio
    Pantelias, Antonio
    Pepe, Gaetano
    Ricoul, Michelle
    Sabatier, Laure
    Sebastia, Natividad
    Sommer, Sylwester
    Vral, Anne
    Zafiropoulos, Demetre
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Jan Kochanowski University, Poland.
    Dose assessment intercomparisons within the RENEB network using G(0)-lymphocyte prematurely condensed chromosomes (PCC assay)2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 48-57Article in journal (Refereed)
    Abstract [en]

    Purpose: Dose assessment intercomparisons within the RENEB network were performed for triage biodosimetry analyzing G(0)-lymphocyte PCC for harmonization, standardization and optimization of the PCC assay. Materials and methods: Comparative analysis among different partners for dose assessment included shipment of PCC-slides and captured images to construct dose-response curves for up to 6 Gy gamma-rays. Accident simulation exercises were performed to assess the suitability of the PCC assay by detecting speed of analysis and minimum number of cells required for categorization of potentially exposed individuals. Results: Calibration data based on Giemsa-stained fragments in excess of 46 PCC were obtained by different partners using galleries of PCC images for each dose-point. Mean values derived from all scores yielded a linear dose-response with approximately 4 excess-fragments/cell/Gy. To unify scoring criteria, exercises were carried out using coded PCC-slides and/or coded irradiated blood samples. Analysis of samples received 24h post-exposure was successfully performed using Giemsa staining (1 excess-fragment/cell/Gy) or centromere/telomere FISH-staining for dicentrics. Conclusions: Dose assessments by RENEB partners using appropriate calibration curves were mostly in good agreement. The PCC assay is quick and reliable for whole- or partial-body triage biodosimetry by scoring excess-fragments or dicentrics in G(0)-lymphocytes. Particularly, analysis of Giemsa-stained excess PCC-fragments is simple, inexpensive and its automation could increase throughput and scoring objectivity of the PCC assay.

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