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  • 151.
    Gupta, Vikas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lantz, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Henriksson, Lilian
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Karlsson, Matts
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Persson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Automated three-dimensional tracking of the left ventricular myocardium in time-resolved and dose-modulated cardiac CT images using deformable image registration2018In: Journal of Cardiovascular Computed Tomography, ISSN 1934-5925, Vol. 12, no 2, p. 139-148Article in journal (Refereed)
    Abstract [en]

    Background Assessment of myocardial deformation from time-resolved cardiac computed tomography (4D CT) would augment the already available functional information from such an examination without incurring any additional costs. A deformable image registration (DIR) based approach is proposed to allow fast and automatic myocardial tracking in clinical 4D CT images.

    Methods Left ventricular myocardial tissue displacement through a cardiac cycle was tracked using a B-spline transformation based DIR. Gradient of such displacements allowed Lagrangian strain estimation with respect to end-diastole in clinical 4D CT data from ten subjects with suspected coronary artery disease. Dice similarity coefficient (DSC), point-to-curve error (PTC), and tracking error were used to assess the tracking accuracy. Wilcoxon signed rank test provided significance of tracking errors. Topology preservation was verified using Jacobian of the deformation. Reliability of estimated strains and torsion (normalized twist angle) was tested in subjects with normal function by comparing them with normal strain in the literature.

    Results Comparison with manual tracking showed high accuracy (DSC: 0.99± 0.05; PTC: 0.56mm± 0.47 mm) and resulted in determinant(Jacobian) > 0 for all subjects, indicating preservation of topology. Average radial (0.13 mm), angular (0.64) and longitudinal (0.10 mm) tracking errors for the entire cohort were not significant (p > 0.9). For patients with normal function, average strain [circumferential, radial, longitudinal] and peak torsion estimates were: [-23.5%, 31.1%, −17.2%] and 7.22°, respectively. These estimates were in conformity with the reported normal ranges in the existing literature.

    Conclusions Accurate wall deformation tracking and subsequent strain estimation are feasible with the proposed method using only routine time-resolved 3D cardiac CT.

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  • 152.
    Gustafsson, Agneta
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Karlsson, Henrik
    Kalmar County Hospital, Sweden.
    Nilsson, Kerstin A.
    Geijer, Hakan
    Örebro University Hospital, Sweden.
    Olsson, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    A visual grading study for different administered activity levels in bone scintigraphy2015In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 35, no 3, p. 231-236Article in journal (Refereed)
    Abstract [en]

    IntroductionThe aim of the study is to assess the administered activity levels versus visual-based image quality using visual grading regression (VGR) including an assessment of the newly stated image criteria for whole-body bone scintigraphy. Materials and methodsA total of 90 patients was included and grouped in three levels of administered activity: 400, 500 and 600 MBq. Six clinical image criteria regarding image quality was formulated by experienced nuclear medicine physicians. Visual grading was performed in all images, where three physicians rated the fulfilment of the image criteria on a four-step ordinal scale. The results were analysed using VGR. A count analysis was also made where the total number of counts in both views was registered. ResultsThe administered activity of 600 MBq gives significantly better image quality than 400 MBq in five of six criteria (Pless than005). Comparing the administered activity of 600 MBq to 500 MBq, four criteria of six show significantly better image quality (Pless than005). The administered activity of 500 MBq gives no significantly better image quality than 400 Mbq (Pless than005). The count analysis shows that none of the three levels of administrated activity fulfil the recommendations by the EANM. ConclusionThere was a significant improvement in perceived image quality using an activity level of 600 MBq compared to lower activity levels in whole-body bone scintigraphy for the gamma camera equipment end set-up used in this study. This type of visual-based grading study seems to be a valuable tool and easy to implement in the clinical environment.

  • 153.
    Gustafsson, Håkan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Biomedical Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Lindgren, Mikael
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology. Norwegian University of Science and Technology, Norway.
    Kolbun, Natallia
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jonson, Maria
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    de Muinck, Ebo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Visualization of oxidative stress in ex vivo biopsies using electron paramagnetic resonance imaging2015In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 73, no 4, p. 1682-1691Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies.

    METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections.

    RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques.

    CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique. Magn Reson Med, 2014.

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  • 154.
    Gustafsson, Håkan
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Norell, M.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Lindgren, Mikael
    Norwegian University of Science and Technology, Trondheim, Norway.
    Engström, Maria
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Zachrisson, Helene
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Fe(III) distribution varies substantially within and between atherosclerotic plaques2014In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 2, no 71, p. 885-892Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    Vulnerable atherosclerotic plaques are structurally weak and prone to rupture, presumably due to local oxidative stress. Redox active iron is linked to oxidative stress and the aim of this study was to investigate the distribution of Fe(III) in carotid plaques and its relation to vulnerability for rupture.

    METHODS:

    Atherosclerotic plaques from 10 patients (three asymptomatic and seven symptomatic) were investigated. Plaque vulnerability was classified using ultrasound and immunohistochemistry and correlated to Fe(III) measured by electron paramagnetic resonance spectroscopy.

    RESULTS:

    Large intra-plaque Fe(III) variations were found. Plaques from symptomatic patients had a higher Fe(III) concentration as compared with asymptomatic plaques (0.36 ± 0.21 vs. 0.06 ± 0.04 nmol Fe(III)/mg tissue, P < 0.05, in sections adjoining narrowest part of the plaques). All but one plaque from symptomatic patients showed signs of cap rupture. No plaque from asymptomatic patients showed signs of cap rupture. There was a significant increase in cap macrophages in plaques from symptomatic patients compared with asymptomatic patients (31 ± 11% vs. 2.3 ± 2.3%, P < 0.01).

    CONCLUSION:

    Fe(III) distribution varies substantially within atherosclerotic plaques. Plaques from symptomatic patients had significantly higher concentrations of Fe(III), signs of cap rupture and increased cap macrophage activity.

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  • 155.
    Gustafsson, Håkan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Norrköping/Finspång. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Kale, Ajay
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Dasu, Alexandru
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. The Skandion Clinic, Uppsala, Sweden.
    Lund, Anders
    Linköping University, Department of Physics, Chemistry and Biology, Chemical Physics. Linköping University, Faculty of Science & Engineering.
    Edqvist, Per-Henrik
    Uppsala University, Uppsala, Sweden.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    EPR oximetry of cetuximab-treated head-and-neck tumours in a mouse model2017In: Cell Biochemistry and Biophysics, ISSN 1085-9195, E-ISSN 1559-0283, Vol. 75, no 3-4, p. 299-309Article in journal (Refereed)
    Abstract [en]

    Head and neck squamous cell carcinoma (HNSCC) tumours are associated with high mortality despite advances in therapy. The monoclonal antibody cetuximab (Erbitux®) has been approved for the treatment of advanced HNSCC. However, only a subset of HNSC patients receiving cetuximab actually responds to treatment, underlining the need for a means to tailor treatments of individual patients. The aim of the present study was to investigate the effect of cetuximab treatment on tumour growth, on tumour partial oxygen pressure as measured by LiPc electron paramagnetic resonance oximetry and on the expression of proteins involved in tumour growth, metabolism and hypoxia. Two HNSCC cell lines, UT-SCC-2 and UT-SCC-14, were used to generate xenografts on female BALB/c (nu/nu) nude mice. Mice with xenografts were given three injections of intraperitoneal cetuximab or phosphate-buffered saline, and the tumour volume was recorded continuously. After treatment the tumour partial oxygen pressure was measured by LiPc electron paramagnetic resonance oximetry and the expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, Ki-67, MCT1, MCT4, GLUT1, CAIX and HIF-1α were investigated by immunohistochemistry. In xenografts from both cell lines (UT-SCC-2 and UT-SCC-14) cetuximab had effect on the tumour volume but the effect was more pronounced on UT-SCC-14 xenografts. A higher tumour oxygenation was measured in cetuximab-treated tumours from both cell lines compared to untreated controls. Immunocytochemical staining after cetuximab treatment shows a significantly decreased expression of EGFR, pEGFR, Ki67, CAIX and nuclear HIF-1α in UT-SCC-14 tumours compared to untreated controls. MCT1 and GLUT1 were significantly decreased in tumours from both cell lines but more pronounced in UT-SCC-14 tumours. Taken together, our results show that cetuximab treatment decreases the tumour growth and increases the tumour partial oxygen pressure of HNSCC xenografts. Furthermore we found a potential connection between the partial oxygen pressure of the tumours and the expression of proteins involved in tumour growth, metabolism and hypoxia.

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  • 156.
    Gustafsson, Mikael
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, The Institute of Technology.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Absolut kvantifiering av metaboliter i hjärnans vita substans hos patienter med MS och normal magnetkamerundersökning2000Conference paper (Other academic)
  • 157.
    Hadimeri, Ursula
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Department of Radiology, Kärnsjukhuset, Skövde, Sverige.
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Fransson, Sven-Göran
    Public Health and Clinical Medicine, Umea University, Umea - Sweden.
    Stegmayr, Bernd
    Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Hadimeri, Henrik
    Department of Nephrology, Kärnsjukhuset, Skövde, Sweden.
    Fistula diameter correlates with echocardiographic characteristics in stable hemodialysis patients2015In: Nephrology @ Point of Care, ISSN 2059-3007, Vol. 1, no 1, p. e44-e48Article in journal (Refereed)
    Abstract [en]

    Left ventricular hypertrophy (LVH) is a common finding in hemodialysis patients. The aim of the present study was to investigate if the diameter of the distal radiocephalic fistula could influence left ventricular variables in stable hemodialysis patients.

    Methods

    Nineteen patients were investigated. Measurements of the diameter of the arteriovenous (AV) fistula were performed in 4 different locations. The patients were investigated using M-mode recordings and measurements in the 2D image. Doppler ultrasound was also performed. Transonic measurements were performed after ultrasound investigation.

    Results

    Fistula mean and maximal diameter correlated with left ventricular characteristics. Fistula flow correlated neither with the left ventricular characteristics nor with fistula diameters.

    Conclusions

    The maximal diameter of the distal AV fistula seems to be a sensitive marker of LVH in stable hemodialysis patients.

  • 158.
    Hadimeri, Ursula
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Skaraborg Hosp, Sweden.
    Warme, Anna
    Univ Gothenburg, Sweden; Skaraborg Hosp, Sweden.
    Nasic, Salmir
    Skaraborg Hosp, Sweden.
    Fransson, Sven Göran
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Wigelius, Ann
    Umea Univ, Sweden.
    Stegmayr, Bernd
    Umea Univ, Sweden.
    Angiography and phlebography in a hemodialysis population: A retrospective analysis of interventional results2019In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 42, no 12, p. 675-683Article in journal (Refereed)
    Abstract [en]

    Objective: To clarify the reasons and beneficial effects and duration of arteriovenous fistula patency after radiological interventions in arteriovenous fistula. The patients investigated were referred due to arteriovenous fistula access flow problems. Material and methods: In 174 patients, 522 radiological investigations and endovascular treatments such as percutaneous transluminal angioplasty were analyzed, retrospectively. All investigations were performed due to clinical suspicion of impaired arteriovenous fistula function. Results: Arterial stenosis was significantly more frequent among patients with diabetic nephropathy (p amp;lt; 0.001) and interstitial nephritis (p amp;lt; 0.001). According to the venous stenosis, the diagnosis did not affect the frequency (p = 0.22) or the degree (p = 0.39) of stenosis. The degree of stenosis prior to percutaneous transluminal angioplasty correlated significantly with the degree of remaining stenosis after intervention (p amp;lt; 0.001). Of the 174 patients, 123 (71%) performed a total of 318 investigations including percutaneous transluminal angioplasty. Repeated percutaneous transluminal angioplasty was performed significantly more often in patients with diabetic nephropathy. The median times to the first percutaneous transluminal angioplasty and to the subsequent percutaneous transluminal angioplasties were 9.5 and 5 months, respectively. Arteriovenous fistula in patients with diabetic nephropathy performed similar to most other diagnoses, although performing more percutaneous transluminal angioplasty/patient than most other diagnoses. Conclusion: Many patients could maintain long-term patency of arteriovenous fistula, including those with diabetic nephropathy, with repeated interventions; this motivates a closer follow-up for these patients. Clinically significant stenosis should be dilated as meticulously and as soon as possible. Occlusions of the arteriovenous fistula in most instances can be successfully thrombolyzed or dilated upon early diagnosis.

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  • 159.
    Halilic, Senija
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Kämmerling, Nina
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Värdet av DT-buköversikt som primär undersökning vid akut buksmärta2016Report (Other academic)
    Abstract [sv]

    Syftet med studien var att se hur stor andel av de patienter som genomgått DT-BÖS vid akut påkomna buksymptom som behöver genomgå kompletterande undersökning, samt vilken diagnos som ställdes vid den kompletterande undersökningen. Vilka frågeställningar besvarar DT-BÖS vid akut påkommen buksmärta? Vilka frågeställningar motiverar annan  undersökning som förstahandsundersökning?

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    Värdet av DT-buköversikt som primär undersökning vid akut buksmärta
  • 160.
    Hansson, Edvin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Westinghouse Electric Sweden AB, Västerås, Sweden.
    Pettersson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Fortin, C
    Carl Zeiss SAS, Marley-le-Roi, France.
    Eriksson, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Swedish Radiation Safety Authority, Stockholm, Sweden.
    Uranium aerosols at a nuclear fuel fabrication plant: Characterization using scanning electron microscopy and energy dispersive X-ray spectroscopy2017In: Spectrochimica Acta Part B - Atomic Spectroscopy, ISSN 0584-8547, E-ISSN 1873-3565, p. 130-137Article in journal (Refereed)
    Abstract [en]

    Detailed aerosol knowledge is essential in numerous applications, including risk assessment in nuclear industry. Cascade impactor sampling of uranium aerosols in the breathing zone of nuclear operators was carried out at a nuclear fuel fabrication plant. Collected aerosols were evaluated using scanning electron microscopy and energy dispersive X-ray spectroscopy. Imaging revealed remarkable variations in aerosol morphology at the different workshops, and a presence of very large particles (up to ≅ 100 × 50 μm2) in the operator breathing zone. Characteristic X-ray analysis showed varying uranium weight percentages of aerosols and, frequently, traces of nitrogen, fluorine and iron. The analysis method, in combination with cascade impactor sampling, can be a powerful tool for characterization of aerosols. The uranium aerosol source term for risk assessment in nuclear fuel fabrication appears to be highly complex.

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  • 161.
    Haufe, William
    et al.
    Department of Radiology, University of California, San Diego, San Diego, CA, United states.
    Hooker, Jonathan
    Department of Radiology, University of California, San Diego, San Diego, CA, United States.
    Schlein, Alexandra
    Department of Radiology, University of California, San Diego, San Diego, CA, United States.
    Szeverenyi, Nikolaus
    Department of Radiology, University of California, San Diego, San Diego, CA, United States.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Advanced MR Analytics AB, Linköping, Sweden.
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Advanced MR Analytics AB, Linköping, Sweden.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Advanced MR Analytics AB, Linköping, Sweden.
    Tunón, Patrik
    Advanced MR Analytics AB, Linköping, Sweden.
    Horgan, Santiago
    Surgery, University of California, San Diego, San Diego, CA, United States.
    Jacobsen, Garth
    Surgery, University of California, San Diego, San Diego, CA, United States.
    Schwimmer, Jeffrey B
    University of California, San Diego, San Diego, CA, United States.
    Reeder, Scott B
    University of Wisconsin, Madison, Madison, WI, United States.
    Sirlin, Claude B.
    Department of Radiology, University of California, San Diego, San Diego, CA, United States.
    Feasibility of an automated tissue segmentation technique in a longitudinal weight loss study2016Conference paper (Other academic)
    Abstract [en]

    To address the problems inherent in manual methods, a novel, semi-automated tissue segmentation image analysis technique has been developed. The purpose of this study was to demonstrate the feasibility and describe preliminary observations of applying this technique to quantify and monitor longitudinal changes in abdominal adipose tissue and thigh muscle volume in obese adults during weight loss. Abdominal adipose tissue and thigh muscle volume decreased during weight loss. As a proportion of body weight, adipose tissue volumes decreased during weight loss. By comparison, as a proportion of body weight, thigh muscle volume increased.

  • 162.
    Hermsen, Meyke
    et al.
    Radboud Univ Nijmegen, Netherlands.
    de Bel, Thomas
    Radboud Univ Nijmegen, Netherlands.
    den Boer, Marjolijn
    Radboud Univ Nijmegen, Netherlands.
    Steenbergen, Eric J.
    Radboud Univ Nijmegen, Netherlands.
    Kers, Jesper
    Univ Amsterdam, Netherlands; Univ Amsterdam, Netherlands; Ragon Inst Massachusetts Gen Hosp Massachusetts I, MA USA.
    Florquin, Sandrine
    Univ Amsterdam, Netherlands.
    Roelofs, Joris J. T. H.
    Univ Amsterdam, Netherlands.
    Stegall, Mark D.
    Mayo Clin, MN USA; Mayo Clin, MN USA.
    Alexander, Mariam P.
    Mayo Clin, MN USA; Mayo Clin, MN USA.
    Smith, Byron H.
    Mayo Clin, MN USA; Mayo Clin, MN USA.
    Smeets, Bart
    Radboud Univ Nijmegen, Netherlands.
    Hilbrands, Luuk B.
    Radboud Univ Nijmegen, Netherlands.
    van der Laak, Jeroen
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Radboud Univ Nijmegen, Netherlands.
    Deep Learning-Based Histopathologic Assessment of Kidney Tissue2019In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 30, no 10, p. 1968-1979Article in journal (Refereed)
    Abstract [en]

    Background The development of deep neural networks is facilitating more advanced digital analysis of histopathologic images. We trained a convolutional neural network for multiclass segmentation of digitized kidney tissue sections stained with periodic acid-Schiff (PAS). Methods We trained the network using multiclass annotations from 40 whole-slide images of stained kidney transplant biopsies and applied it to four independent data sets. We assessed multiclass segmentation performance by calculating Dice coefficients for ten tissue classes on ten transplant biopsies from the Radboud University Medical Center in Nijmegen, The Netherlands, and on ten transplant biopsies from an external center for validation. We also fully segmented 15 nephrectomy samples and calculated the networks glomerular detection rates and compared network-based measures with visually scored histologic components (Banff classification) in 82 kidney transplant biopsies. Results The weighted mean Dice coefficients of all classes were 0.80 and 0.84 in ten kidney transplant biopsies from the Radboud center and the external center, respectively. The best segmented class was "glomeruli" in both data sets (Dice coefficients, 0.95 and 0.94, respectively), followed by "tubuli combined" and "interstitium." The network detected 92.7% of all glomeruli in nephrectomy samples, with 10.4% false positives. In whole transplant biopsies, the mean intraclass correlation coefficient for glomerular counting performed by pathologists versus the network was 0.94. We found significant correlations between visually scored histologic components and network-based measures. Conclusions This study presents the first convolutional neural network for multiclass segmentation of PAS-stained nephrectomy samples and transplant biopsies. Our network may have utility for quantitative studies involving kidney histopathology across centers and provide opportunities for deep learning applications in routine diagnostics.

  • 163.
    Hlawitschka, Mario
    et al.
    Department of Computer Science, Leipzig University, Germany.
    Hotz, Ingrid
    Zuse Institue Berlin, Germany.
    Kratz, Andrea
    Zuse Institue Berlin, Germany.
    Marai, G. Elisabeta
    Department of Computer Science, University of Pittsburgh, USA.
    Moreno, Rodrigo
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Scheuermann, Gerik
    Department of Computer Science, Leipzig University, Germany.
    Strommel, Markus
    Chair of Polymer Materials, Saarland University, Saarbruecken, Germany.
    Wiebel, Alexander
    Department of Electrical Engineering and Computer Sciences, Coburg University of Applied Sciences, Germany.
    Zhang, Eugene
    School of Electrical Engineering and Computer Science, Oregon State University, Corvallis, USA.
    Top Challenges in the Visualization of Engineering Tensor Fields2014In: Visualization and Processing of Tensors and Higher Order Descriptors for Multi-Valued Data / [ed] Carl-Fredrik Westin, Anna Vilanova, Bernhard Burgeth, Springer Berlin/Heidelberg, 2014, p. 3-15Chapter in book (Refereed)
    Abstract [en]

    In this chapter we summarize the top research challenges in creating successful visualization tools for tensor fields in engineering. The analysis is based on our collective experiences and on discussions with both domain experts and visualization practitioners. We find that creating visualization tools for engineering tensors often involves solving multiple different technical problems at the same time—including visual intuitiveness, scalability, interactivity, providing both detail and context, integration with modeling and simulation, representing uncertainty and managing multi-fields; as well as overcoming terminology barriers and advancing research in the mathematical aspects of tensor field processing. We further note the need for tools and data repositories to encourage faster advances in the field. Our interest in creating and proposing this list is to initiate a discussion about important research issues within the visualization of engineering tensor fields.

  • 164. Ho, C
    et al.
    Hunte, G
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Vogel, HJ
    Multinuclear NMR studies on erythrocyte storage1986Conference paper (Other academic)
  • 165. Ho, C
    et al.
    Hunte, G
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Vogel, HJ
    Multinuclear NMR studies on erythrocytes1986Conference paper (Other academic)
  • 166.
    Holm, Åsa
    et al.
    Linköping University, Department of Mathematics, Optimization . Linköping University, Faculty of Science & Engineering.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Larsson, Torbjörn
    Linköping University, Department of Mathematics, Optimization . Linköping University, The Institute of Technology.
    Heuristics for Integrated Optimization of Catheter Positioning and Dwell Time Distribution in Prostate HDR Brachytherapy2016In: Annals of Operations Research, ISSN 0254-5330, E-ISSN 1572-9338, Vol. 236, no 2, p. 319-339Article in journal (Refereed)
    Abstract [en]

    High dose-rate (HDR) brachytherapy is a kind of radiotherapy used to treat, among others, prostate cancer. When applied to prostate cancer a radioactive source is moved through catheters implanted into the prostate. For each patient a treatment plan is constructed that decide for example catheter placement and dwell time distribution, that is where to stop the radioactive source and for how long.

    Mathematical optimization methods has been used to find quality plans with respect to dwell time distribution, however few optimization approaches regarding catheter placement have been studied. In this article we present an integrated optimization model that optimize catheter placement and dwell time distribution simultaneously. Our results show that integrating the two decisions yields greatly improved plans, from 15% to 94% improvement.

    Since the presented model is computationally demanding to solve we also present three heuristics: tabu search, variable neighbourhood search and genetic algorithm. Of these variable neighbourhood search is clearly the best, outperforming a state-of-the-art optimization software (CPLEX) and the two other heuristics.

  • 167.
    Holm, Åsa
    et al.
    Linköping University, Department of Mathematics, Optimization . Linköping University, The Institute of Technology.
    Larsson, Torbjörn
    Linköping University, Department of Mathematics, Optimization . Linköping University, The Institute of Technology.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    A linear programming model for optimizing HDR brachytherapy dose distributions with respect to mean dose in the DVH-tail2013In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 40, no 8Article in journal (Refereed)
    Abstract [en]

    Purpose: Recent research has shown that the optimization model hitherto used in high-dose-rate (HDR) brachytherapy corresponds weakly to the dosimetric indices used to evaluate the quality of a dose distribution. Although alternative models that explicitly include such dosimetric indices have been presented, the inclusion of the dosimetric indices explicitly yields intractable models. The purpose of this paper is to develop a model for optimizing dosimetric indices that is easier to solve than those proposed earlier. less thanbrgreater than less thanbrgreater thanMethods: In this paper, the authors present an alternative approach for optimizing dose distributions for HDR brachytherapy where dosimetric indices are taken into account through surrogates based on the conditional value-at-risk concept. This yields a linear optimization model that is easy to solve, and has the advantage that the constraints are easy to interpret and modify to obtain satisfactory dose distributions. less thanbrgreater than less thanbrgreater thanResults: The authors show by experimental comparisons, carried out retrospectively for a set of prostate cancer patients, that their proposed model corresponds well with constraining dosimetric indices. All modifications of the parameters in the authors model yield the expected result. The dose distributions generated are also comparable to those generated by the standard model with respect to the dosimetric indices that are used for evaluating quality. less thanbrgreater than less thanbrgreater thanConclusions: The authors new model is a viable surrogate to optimizing dosimetric indices and quickly and easily yields high quality dose distributions.

  • 168.
    Holm, Åsa
    et al.
    Linköping University, Department of Mathematics, Optimization . Linköping University, The Institute of Technology.
    Larsson, Torbjörn
    Linköping University, Department of Mathematics, Optimization . Linköping University, The Institute of Technology.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Study of the Relationship Between Dosimetric Indices and Linear Penalties in Dose Distribution Optimization for HDR Prostate Brachytherapy2013Manuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: Most clinical software for optimizing dwelling time patterns is based on a linear penalty model. The quality of a dose distribution generated by the dwelling time pattern is, however, evaluated through a number of dosimetric indices. The purpose of this article is to investigate the relationship between the linear penalty model and the dosimetric indices.

    Method and Materials: Data sets from three patients, previously treated for prostate cancer with HDR brachytherapy as a boost to external beam therapy, were used for this study, and for each of them 300 random dwelling time patterns were generated. The relationship between the linear penalty model and the dosimetric indices were studied both by the Pearson’s product moment correlation coefficient between the objective function value of the linear penalty model and the values of the dosimetric indices, and by scatter-grams.

    Results: For one of the three patients we found a clear connection between the linear penalty model and the values of the dosimetric indices, but not for the other two. For the two patients without a clear connection there where some dosimetric indices that actually improved with deteriorating objective function value.

    Conclusion: The dwelling time pattern found by using the linear penalty model does not correspond to the optimal dose distribution with respect to dosimetric indices.

  • 169.
    Homeyer, Andre
    et al.
    Fraunhofer MEVIS, Germany.
    Nasr, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Engel, Christiane
    Fraunhofer MEVIS, Germany.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ekstedt, Mattias
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Kost, Henning
    Fraunhofer MEVIS, Germany.
    Weiss, Nick
    Fraunhofer MEVIS, Germany.
    Palmer, Tim
    University of Leeds, England.
    Karl Hahn, Horst
    Fraunhofer MEVIS, Germany.
    Treanor, Darren
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. University of Leeds, England; Leeds Teaching Hospital NHS Trust, England.
    Lundström, Claes
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Automated quantification of steatosis: agreement with stereological point counting2017In: Diagnostic Pathology, ISSN 1746-1596, E-ISSN 1746-1596, Vol. 12, article id 80Article in journal (Refereed)
    Abstract [en]

    Background: Steatosis is routinely assessed histologically in clinical practice and research. Automated image analysis can reduce the effort of quantifying steatosis. Since reproducibility is essential for practical use, we have evaluated different analysis methods in terms of their agreement with stereological point counting (SPC) performed by a hepatologist. Methods: The evaluation was based on a large and representative data set of 970 histological images from human patients with different liver diseases. Three of the evaluated methods were built on previously published approaches. One method incorporated a new approach to improve the robustness to image variability. Results: The new method showed the strongest agreement with the expert. At 20x resolution, it reproduced steatosis area fractions with a mean absolute error of 0.011 for absent or mild steatosis and 0.036 for moderate or severe steatosis. At 10x resolution, it was more accurate than and twice as fast as all other methods at 20x resolution. When compared with SPC performed by two additional human observers, its error was substantially lower than one and only slightly above the other observer. Conclusions: The results suggest that the new method can be a suitable automated replacement for SPC. Before further improvements can be verified, it is necessary to thoroughly assess the variability of SPC between human observers.

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  • 170.
    Hricak, Hedvig
    et al.
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Ringertz, Hans
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Thrall, James H.
    Massachusetts Gen Hospital, MA 02114 USA.
    Dixon, Adrian K.
    Addenbrookes Hospital, England.
    Arenson, Ronald L.
    University of Calif San Francisco, CA 94143 USA.
    Bradley, William G.
    University of Calif San Diego, CA 92103 USA.
    Muellner, Ada
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Krestin, Gabriel P.
    University of Rotterdam Hospital, Netherlands.
    Editorial Material: When Vision Prevails: A History of the International Society for Strategic Studies in Radiology in JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY, vol 12, issue 10, pp 1112-11142015In: Journal of the American College of Radiology, ISSN 1546-1440, E-ISSN 1558-349X, Vol. 12, no 10, p. 1112-1114Article in journal (Other academic)
    Abstract [en]

    n/a

  • 171.
    Hu, Zhangjun
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Ahrén, Maria
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Selegård, Linnéa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Skoglund, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Söderlind, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Engström, Maria
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Xuanjun
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Highly Water-Dispersible Surface-Modified Gd2O3 Nanoparticles for Potential Dual-Modal Bioimaging2013In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, no 38, p. 12658-12667Article in journal (Refereed)
    Abstract [en]

    Water-dispersible and luminescent gadolinium oxide (GO) nanoparticles (NPs) were designed and synthesized for potential dual-modal biological imaging. They were obtained by capping gadolinium oxide nanoparticles with a fluorescent glycol-based conjugated carboxylate (HL). The obtained nanoparticles (GO-L) show long-term colloidal stability and intense blue fluorescence. In addition, L can sensitize the luminescence of europium(III) through the so-called antenna effect. Thus, to extend the spectral ranges of emission, europium was introduced into L-modified gadolinium oxide nanoparticles. The obtained Eu-III-doped particles (Eu:GO-L) can provide visible red emission, which is more intensive than that without L capping. The average diameter of the monodisperse modified oxide cores is about 4nm. The average hydrodynamic diameter of the L-modified nanoparticles was estimated to be about 13nm. The nanoparticles show effective longitudinal water proton relaxivity. The relaxivity values obtained for GO-L and Eu:GO-L were r(1)=6.4 and 6.3s(-1)mM(-1) with r(2)/r(1) ratios close to unity at 1.4T. Longitudinal proton relaxivities of these nanoparticles are higher than those of positive contrast agents based on gadolinium complexes such as Gd-DOTA, which are commonly used for clinical magnetic resonance imaging. Moreover, these particles are suitable for cellular imaging and show good biocompatibility.

  • 172.
    Håkansson, Irene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Cassel, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Blennow, K.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Zetterberg, H.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden; UCL Institute Neurol, England.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing-remitting multiple sclerosis2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, no 5, p. 703-712Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis (MS). We assessed whether neurodegenerative and neuroinflammatory markers in cerebrospinal fluid (CSF) at initial sampling could predict disease activity during 2 years of follow-up in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS. Methods: Using multiplex bead array and enzyme-linked immunosorbent assay, CXCL1, CXCL8, CXCL10, CXCL13, CCL20, CCL22, neurofilament light chain (NFL), neurofilament heavy chain, glial fibrillary acidic protein, chitinase-3-like-1, matrix metalloproteinase-9 and osteopontin were analysed in CSF from 41 patients with CIS or relapsing-remitting MS and 22 healthy controls. Disease activity (relapses, magnetic resonance imaging activity or disability worsening) in patients was recorded during 2 years of follow-up in this prospective longitudinal cohort study. Results: In a logistic regression analysis model, NFL in CSF at baseline emerged as the best predictive marker, correctly classifying 93% of patients who showed evidence of disease activity during 2 years of follow-up and 67% of patients who did not, with an overall proportion of 85% (33 of 39 patients) correctly classified. Combining NFL with either neurofilament heavy chain or osteopontin resulted in 87% overall correctly classified patients, whereas combining NFL with a chemokine did not improve results. Conclusions: This study demonstrates the potential prognostic value of NFL in baseline CSF in CIS and relapsing-remitting MS and supports its use as a predictive biomarker of disease activity.

  • 173.
    Håkansson, Irene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Cassel, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Blennow, Kaj
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Zetterberg, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; UCL Inst Neurol, England; UCL, England.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Neurofilament levels, disease activity and brain volume during follow-up in multiple sclerosis2018In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 15, article id 209Article in journal (Refereed)
    Abstract [en]

    Background: There is a need for clinically useful biomarkers of disease activity in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS). The aim of this study was to assess the correlation between neurofilament light chain (NFL) in cerebrospinal fluid (CSF) and serum and the relationship between NFL and other biomarkers, subsequent disease activity, and brain volume loss in CIS and RRMS. Methods: A panel of neurodegenerative and neuroinflammatory markers were analyzed in repeated CSF samples from 41 patients with CIS or RRMS in a prospective longitudinal cohort study and from 22 healthy controls. NFL in serum was analyzed using a single-molecule array (Simoa) method. "No evidence of disease activity-3" (NEDA-3) status and brain volume (brain parenchymal fraction calculated using SyMRI (R)) were recorded during 4 years of follow-up. Results: NFL levels in CSF and serum correlated significantly (all samples, n = 63, r 0.74, p amp;lt; 0.001), but CSF-NFL showed an overall stronger association profile with NEDA-3 status, new T2 lesions, and brain volume loss. CSF-NFL was associated with both new T2 lesions and brain volume loss during follow-up, whereas CSF-CHI3L1 was associated mainly with brain volume loss and CXCL1, CXCL10, CXCL13, CCL22, and MMP-9 were associated mainly with new T2 lesions. Conclusions: Serum and CSF levels of NFL correlate, but CSF-NFL predicts and reflects disease activity better than S-NFL. CSF-NFL levels are associated with both new T2 lesions and brain volume loss. Our findings further add to the accumulating evidence that CSF-NFL is a clinically useful biomarker in CIS and RRMS and should be considered in the expanding NEDA concept. CSF-CXCL10 and CSF-CSF-CHI3L1 are potential markers of disease activity and brain volume loss, respectively.

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  • 174.
    Höök, Fredrik
    et al.
    Chalmers tekniska högskola, Sweden .
    Persson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Kasemo, Bengt
    Chalmers tekniska högskola, Sweden.
    Nanopartiklar kan förbättra avbildningsteknik och diagnostik2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114Article, review/survey (Refereed)
    Abstract [en]

    Nanotechnology can improve diagnostics The unique properties of nanoparticles make them tailorable into diagnostic agents on a molecular level, which allow more sensitive and precise in vitro diagnostics and in vivo imaging. While in vitro applications already have impact on diagnostics, in vivo use remains challenging due to difficulties in preparing nanoparticles with acceptable properties regarding toxicity, specific target accumulation and degradation. This article describes the innovative work of developing such platforms, and concludes that while nanotechnology-based diagnostics and imaging are still scarce at the clinical level, the rapid development of many new concepts, devices and processes that are now in the laboratory pipeline promises significant impact in the near future.

  • 175.
    Icenhour, Adriane
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tapper, Sofie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bednarska, Olga
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Witt, Suzanne Tyson
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Elsenbruch, Sigrid
    Univ Duisburg Essen, Germany.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Elucidating the putative link between prefrontal neurotransmission, functional connectivity, and affective symptoms in irritable bowel syndrome2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 13590Article in journal (Refereed)
    Abstract [en]

    Altered neural mechanisms are well-acknowledged in irritable bowel syndrome (IBS), a disorder of brain-gut-communication highly comorbid with anxiety and depression. As a key hub in corticolimbic inhibition, medial prefrontal cortex (mPFC) may be involved in disturbed emotion regulation in IBS. However, aberrant mPFC excitatory and inhibitory neurotransmission potentially contributing to psychological symptoms in IBS remains unknown. Using quantitative magnetic resonance spectroscopy (qMRS), we compared mPFC glutamate + glutamine (Glx) and gamma-aminobutyric acid (GABA+) concentrations in 64 women with IBS and 32 age-matched healthy women (HCs) and investigated their association with anxiety and depression in correlational and subgroup analyses. Applying functional magnetic resonance imaging (fMRI), we explored whether altered neurotransmission was paralleled by aberrant mPFC resting-state functional connectivity (FC). IBS patients did not differ from HCs with respect to mPFC GABA+ or Glx levels. Anxiety was positively associated with mPFC GABA+ concentrations in IBS, whereas Glx was unrelated to psychological or gastrointestinal symptoms. Subgroup comparisons of patients with high or low anxiety symptom severity and HCs revealed increased GABA+ in patients with high symptom severity, and lower mPFC FC with adjacent anterior cingulate cortex (ACC), a crucial region of emotion modulation. Our findings provide novel evidence that altered prefrontal inhibitory neurotransmission may be linked to anxiety in IBS.

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  • 176.
    Icenhour, Adriane
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Witt, Suzanne
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Elsenbruch, Sigrid
    University of Duisburg Essen, Germany.
    Lowén, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tillisch, Kirsten
    University of Calif Los Angeles, CA USA.
    Mayer, Emeran A.
    University of Calif Los Angeles, CA USA.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Brain functional connectivity is associated with visceral sensitivity in women with Irritable Bowel Syndrome2017In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 15, p. 449-457Article in journal (Refereed)
    Abstract [en]

    Increased perception of visceral stimuli is a key feature of Irritable Bowel Syndrome (IBS). While altered resting-state functional connectivity (rsFC) has been also reported in IBS, the relationship between visceral hypersensitivity and aberrant rsFC is unknown. We therefore assessed rsFC within the salience, sensorimotor and default mode networks in patients with and without visceral hypersensitivity and in healthy controls (HCs). An exploratory resting-state functional magnetic resonance imaging study was performed in 41 women with IBS and 20 HCs. Group independent component analysis was used to derive intrinsic brain networks. Rectal thresholds were determined and patients were subdivided into groups with increased (hypersensitive IBS, N = 21) or normal (normosensitive IBS, N= 20) visceral sensitivity. Between-group comparisons of rsFC were carried-out using region-of-interest analyses and peak rsFC values were extracted for correlational analyses. Relative to normosensitive IBS, hypersensitive patients showed increased positive rsFC of pregenual anterior cingulate cortex and thalamus within the salience network and of posterior insula within the sensorimotor network. When compared to both hypersensitive IBS and HCs, normosensitive IBS showed decreased positive rsFC of amygdala and decreased negative rsFC in dorsal anterior insula within the DMN. DMN and sensorimotor network rsFC were associated with rectal perception thresholds, and rsFC in posterior insula was correlated with reported symptom severity in IBS. Our exploratory findings suggest that visceral sensitivity in IBS is related to changes in FC within resting-state networks associated with interoception, salience and sensory processing. These alterations may play an important role in hypervigilance and hyperalgesia in IBS.

  • 177.
    Isaksson, Mats
    et al.
    Univ Gothenburg, Sweden.
    Broggio, David
    IRSN Inst Radioprotect and Surete Nucl, France.
    Fojtik, Pavel
    SURO Natl Radiat Protect Inst, Czech Republic.
    Lebacq, Anne Laure
    SCK CEN Belgian Nucl Res Ctr, Belgium.
    Navarro Amaro, Juan Francisco
    CIEMAT Ctr Invest Energet Medioambientales and Tecn, Spain.
    Osko, Jakub
    Natl Ctr Nucl Res, Poland.
    Perez Lopez, Begona
    CIEMAT Ctr Invest Energet Medioambientales and Tecn, Spain.
    Vu, Isabelle
    IRSN Inst Radioprotect and Surete Nucl, France.
    Battisti, Paolo
    ENEA, Italy.
    Borjesson, Jimmy
    Hallands Sjukhus, Sweden.
    Carlsson, Marie
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Castellani, Carlo Maria
    ENEA, Italy.
    Gårdestig, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Hill, Peter
    Forschungszentrum Julich, Germany.
    Krajewska, Graiyna
    CLOR Cent Lab Radiol Protect, Poland.
    Luenendonk, Guenter
    Forschungszentrum Julich, Germany.
    Meisenberg, Oliver
    BFS, Germany.
    Stenstrom, Mats
    Falu Lasarett, Sweden.
    Ordoulidis, Sokratis El Mantani
    Gavle Sjukhus, Sweden.
    Assessing(131) I in thyroid by non-spectroscopic instruments - A European intercomparison exercise2019In: Radiation Measurements, ISSN 1350-4487, E-ISSN 1879-0925, Vol. 128, article id 106115Article in journal (Refereed)
    Abstract [en]

    One of the issues of the Open Project for the European Radiation Research Area (OPERRA) was human thyroid monitoring in case of a large scale nuclear accident. This issue was covered in task 5.4 as project "CaThyMARA" (Child and Adult Thyroid Monitoring After Reactor Accident), which included several aspects of thyroid monitoring, e.g. screening of facilities able to perform thyroid monitoring in the European countries, dose estimation, modelling of detector response, and two intercomparison exercises. The intercomparison described in this paper focused on thyroid monitoring by non-spectrometric instruments, including gamma cameras and other instruments that were considered available for measurements made by members of the public. A total of 12 facilities from 7 European countries have participated and 43 various measuring devices have been evaluated. The main conclusion of this intercomparison is that the ability to make assessments of (131) I activity in the thyroid to the exposed population after an accidental release must, on the average, be considered as good among the European laboratories taking part in this study. This intercomparison also gave the participants the possibility to calibrate the measuring devices for thyroid measurements of children where this procedure was not available before. A comprehensive report of the intercomparison is given.

  • 178. Order onlineBuy this publication >>
    Israelsson, Axel
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Chewing gum and human hair as retrospective dosimeters2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Retrospective dosimeters are sometimes needed after radiological/nuclear (RN) exposures to determine the doses to individuals. Conventional dosimeters may not be at hand or may not be applicable calling for alternative materials.

    The possible exposure situations can be divided into external and internal; the radiation field stems either from outside the body or from a source within. This thesis investigates the possibility to use chewing gum and hair as retrospective dosimeters. The chewing gum would be used after an unexpected radiation event of external type whereas human hair is examined after chronic intake of uranium. Chewing gum containing xylitol and sorbitol was analyzed using electron paramagnetic resonance (EPR) and the hair was analyzed by alphaspectrometry following radiochemistry and by synchrotron radiation microbeam x-ray fluorescence (SR μ-XRF).

    Xylitol and chewing gum (in this particular case, V6) are in the present work found to be valuable dosimeters after unexpected radiation events. The xylitol signal linearity with dose in the interval 0-10 Gy was confirmed (r2=1.00). The doses to the coating of the chewing gums were determined 4-6 days after irradiation with an uncertainty of less than 0.2 Gy (1 SD). Spectral dependence with time after exposure was found, but was, however, minimal between 4-8 days.

    Hair was evaluated and compared with urine as biodosimeter after ingestion and inhalation intake of uranium. Concentrations of 234U and 238U and their activity ratios were measured in the hair, urine and drinking water sampled from 24 drilled bedrock well water users in Östergötland, Sweden, as well as among 8 workers at a nuclear fuel fabrication factory, Westinghouse Electric Sweden. The results show that there is a stronger correlation between the uranium concentrations in the drinking water of the well water and the users’ hair (r2 = 0.50) than with their urine (r2 = 0.21). There is also a stronger correlation between the 234U/238U activity ratios of water and hair (r2 = 0.91) than between water and urine (r2 = 0.56). The individual absorbed fraction of uranium, the ƒ value, calculated as the ratio between the excreted amount of uranium in urine and hair per day and the daily drinking water intake of uranium stretched from 0.002 to 0.10 with a median of 0.023. The uranium concentrations of the fuel factory workers’ hair and urine were also obtained as well as that of personal air sampler (PAS) filters for the determination of inhaled uranium activity. A large day-to-day variation (7-70 Bq d-1) of the inhaled 234U activity was seen over a 6 week period. Over a 12 week period the 234U activity concentration in urine was similarly seen to vary from 2 to 50 mBq kg-1. Four hair samples from the same subject and period showed less variation (100-240 mBq g-1). The uranium inhalation to urine and hair factors finh,u and finh,h were found to be 0.0014 and 0.0002 respectively given by calculations based on the measured PAS, urine and hair data from two individuals. The SR μ-XRF measurements showed that uranium is present in an outer layer of the hair shaft, about 10-15 μm wide. The  measurements also revealed particles containing uranium being present on the surface of unwashed hair shafts. However, the washed hair shafts showed few, if any, particles.

    This thesis concludes that chewing gum and hair can be used as retrospective dosimeters after external radiation and after intake of uranium respectively.

    List of papers
    1. Dose response of xylitol and sorbitol for EPR retrospective dosimetry with applications to chewing gum
    Open this publication in new window or tab >>Dose response of xylitol and sorbitol for EPR retrospective dosimetry with applications to chewing gum
    2013 (English)In: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 154, no 2, p. 133-141Article in journal (Refereed) Published
    Abstract [en]

    The purpose of this investigation was to study the radiation-induced electron paramagnetic resonance signal in sweeteners xylitol and sorbitol for use in retrospective dosimetry. For both sweeteners and chewing gum, the signal changed at an interval of 1–84 d after irradiation with minimal changes after 4–8 d. A dependence on storage conditions was noticed and the exposure of the samples to light and humidity was therefore minimised. Both the xylitol and sorbitol signals showed linearity with dose in the measured dose interval, 0–20 Gy. The dose-response measurements for the chewing gum resulted in a decision threshold of 0.38 Gy and a detection limit of 0.78 Gy. A blind test illustrated the possibility of using chewing gums as a retrospective dosemeter with an uncertainty in the dose determination of 0.17 Gy (1 SD).

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-85528 (URN)10.1093/rpd/ncs174 (DOI)000316968200001 ()22908355 (PubMedID)
    Available from: 2012-11-22 Created: 2012-11-22 Last updated: 2017-12-07
    2. Measurements of 234U and 238U in Hair, Urine, and Drinking Water Among Drilled Bedrock Well Water Users for the Evaluation of Hair as a Biomonitor of Uranium Intake
    Open this publication in new window or tab >>Measurements of 234U and 238U in Hair, Urine, and Drinking Water Among Drilled Bedrock Well Water Users for the Evaluation of Hair as a Biomonitor of Uranium Intake
    2014 (English)In: Health Physics, ISSN 0017-9078, E-ISSN 1538-5159, Vol. 107, no 2, p. 143-149Article in journal (Refereed) Published
    Abstract [en]

    Hair is evaluated and compared with urine as a biomonitor for human intake of uranium. Concentrations of U and U and the activity ratio between them are measured in the hair, urine, and drinking water of 24 drilled bedrock well water users in Östergötland, Sweden. The samples are measured with α-spectrometry after radiochemical preparation using liquid-liquid separation with tributylphosphate. The results show that there is a stronger correlation between the uranium concentrations in the drinking water of each subject and the hair of the subject (r = 0.50) than with the urine (r = 0.21). There is also a stronger correlation between the activity ratios of water and hair (r = 0.91) than between water and urine (r = 0.56). These results imply that hair may serve as a robust indicator of chronic uranium intake. One obvious advantage over sampling urine is that hair samples reflect a much longer excretion period: weeks compared to days. The absorbed fraction of uranium, the f value, is calculated as the ratio between the excreted amount of uranium in urine and hair per day and the daily drinking water intake of uranium. The f values stretch from 0.002 to 0.10 with a median of 0.023.

    Place, publisher, year, edition, pages
    Wolters Kluwer, 2014
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:liu:diva-108889 (URN)10.1097/HP.0000000000000075 (DOI)000338678800005 ()24978285 (PubMedID)
    Available from: 2014-07-11 Created: 2014-07-11 Last updated: 2017-12-05Bibliographically approved
    3. Using Hair as a Bioindicator for Inhalation of Uranium: A Study on Nuclear Fuel Fabrication Workers
    Open this publication in new window or tab >>Using Hair as a Bioindicator for Inhalation of Uranium: A Study on Nuclear Fuel Fabrication Workers
    2014 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Scalp hair is evaluated and compared with urine as a potential biomonitor following inhalation intake of uranium. The samples were collected among eight workers at a nuclear fuel fabrication factory and the sample concentrations of 234U and 238U were analyzed by α-spectrometry after radiochemical preparation using a TBP-based liquidliquid separation method. Personal air samplers (PAS) filters were also analyzed for determination of inhaled uranium activity.

    The results show that there is a large day-to-day variation (7-70 Bq d-1) of the inhaled 234U activity over a 6 week period. A large variation is also seen for the 234U activity concentration among 12 urine samples collected over a 12 week period; (2-50 mBq kg-1). Four hair samples from the same subject and period showed less variation (100-240 mBq g-1) as they reflect the average excretion over a longer period than the periodic urine samples.

    The total inhalation intake and excretion in urine and hair was obtained for two study subjects over a 6 week period. The uranium inhalation to urine and hair factors finh,u and finh,h were 0.0014 and 0.0002 respectively, given by calculations based on the measured PAS, urine and hair data. It has been demonstrated that scalp hair could be a valuable complement to urine as biomonitor of uranium intake.

    Keywords
    Hair, uranium, alpha spectroscopy
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:liu:diva-108890 (URN)
    Available from: 2014-07-11 Created: 2014-07-11 Last updated: 2014-07-11Bibliographically approved
    4. On the Distribution of Uranium in Hair: Non-Destructive Analysis Using SR-μXRF
    Open this publication in new window or tab >>On the Distribution of Uranium in Hair: Non-Destructive Analysis Using SR-μXRF
    2015 (English)In: Spectrochimica Acta Part B - Atomic Spectroscopy, ISSN 0584-8547, E-ISSN 1873-3565, Vol. 108, p. 28-34Article in journal (Refereed) Published
    Abstract [en]

    In the present study the distribution of uranium in single human hair shafts has been evaluated using two synchrotron radiation (SR) based micro X-ray fluorescence techniques; SR μ-XRF and confocal SR μ-XRF. The hair shafts originated from persons that have been exposed to elevated uranium concentrations. Two different groups have been studied, i) workers at a nuclear fuel fabrication factory, exposed mainly by inhalation and ii) owners of drilled bedrock wells exposed by ingestion of water. The measurements were carried out on the FLUO beamline at the synchrotron radiation facility ANKA, Karlsruhe. The experiment was optimized to detect U with a beam size of 6.8 μm × 3 μm beam focus allowing detection down to ppb levels of U in 10 s (SR μ-XRF setup) and 70 s (SR confocal μ-XRF setup) measurements. It was found that the uranium was present in a 10–15 μm peripheral layer of the hair shafts for both groups studied. Furthermore, potential external hair contamination was studied by scanning of unwashed hair shafts from the workers. Sites of very high uranium signal were identified as particles containing uranium. Such particles, were also seen in complementary analyses using variable pressure electron microscope coupled with energy dispersive X-ray analyzer (ESEM–EDX). However, the particles were not visible in washed hair shafts.

    These findings can further increase the understanding of uranium excretion in hair and its potential use as a biomonitor.

    Place, publisher, year, edition, pages
    Elsevier, 2015
    Keywords
    μ-XRF; Hair; Confocal; Uranium; Internal dosimetry
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:liu:diva-108891 (URN)10.1016/j.sab.2015.04.001 (DOI)000355360400005 ()
    Available from: 2014-07-11 Created: 2014-07-11 Last updated: 2017-12-05Bibliographically approved
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    Chewing gum and human hair as retrospective dosimeters
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  • 179.
    Israelsson, Axel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Eriksson, M.
    Swedish Radiation Safety Authority, Stockholm, Sweden.
    Pettersson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    On the Distribution of Uranium in Hair: Non-Destructive Analysis Using SR-μXRF2015In: Spectrochimica Acta Part B - Atomic Spectroscopy, ISSN 0584-8547, E-ISSN 1873-3565, Vol. 108, p. 28-34Article in journal (Refereed)
    Abstract [en]

    In the present study the distribution of uranium in single human hair shafts has been evaluated using two synchrotron radiation (SR) based micro X-ray fluorescence techniques; SR μ-XRF and confocal SR μ-XRF. The hair shafts originated from persons that have been exposed to elevated uranium concentrations. Two different groups have been studied, i) workers at a nuclear fuel fabrication factory, exposed mainly by inhalation and ii) owners of drilled bedrock wells exposed by ingestion of water. The measurements were carried out on the FLUO beamline at the synchrotron radiation facility ANKA, Karlsruhe. The experiment was optimized to detect U with a beam size of 6.8 μm × 3 μm beam focus allowing detection down to ppb levels of U in 10 s (SR μ-XRF setup) and 70 s (SR confocal μ-XRF setup) measurements. It was found that the uranium was present in a 10–15 μm peripheral layer of the hair shafts for both groups studied. Furthermore, potential external hair contamination was studied by scanning of unwashed hair shafts from the workers. Sites of very high uranium signal were identified as particles containing uranium. Such particles, were also seen in complementary analyses using variable pressure electron microscope coupled with energy dispersive X-ray analyzer (ESEM–EDX). However, the particles were not visible in washed hair shafts.

    These findings can further increase the understanding of uranium excretion in hair and its potential use as a biomonitor.

  • 180.
    Israelsson, Axel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Pettersson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Measurements of 234U and 238U in Hair, Urine, and Drinking Water Among Drilled Bedrock Well Water Users for the Evaluation of Hair as a Biomonitor of Uranium Intake2014In: Health Physics, ISSN 0017-9078, E-ISSN 1538-5159, Vol. 107, no 2, p. 143-149Article in journal (Refereed)
    Abstract [en]

    Hair is evaluated and compared with urine as a biomonitor for human intake of uranium. Concentrations of U and U and the activity ratio between them are measured in the hair, urine, and drinking water of 24 drilled bedrock well water users in Östergötland, Sweden. The samples are measured with α-spectrometry after radiochemical preparation using liquid-liquid separation with tributylphosphate. The results show that there is a stronger correlation between the uranium concentrations in the drinking water of each subject and the hair of the subject (r = 0.50) than with the urine (r = 0.21). There is also a stronger correlation between the activity ratios of water and hair (r = 0.91) than between water and urine (r = 0.56). These results imply that hair may serve as a robust indicator of chronic uranium intake. One obvious advantage over sampling urine is that hair samples reflect a much longer excretion period: weeks compared to days. The absorbed fraction of uranium, the f value, is calculated as the ratio between the excreted amount of uranium in urine and hair per day and the daily drinking water intake of uranium. The f values stretch from 0.002 to 0.10 with a median of 0.023.

    Download full text (pdf)
    Fulltext
  • 181.
    Israelsson, Axel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Pettersson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Using Hair as a Bioindicator for Inhalation of Uranium: A Study on Nuclear Fuel Fabrication Workers2014Manuscript (preprint) (Other academic)
    Abstract [en]

    Scalp hair is evaluated and compared with urine as a potential biomonitor following inhalation intake of uranium. The samples were collected among eight workers at a nuclear fuel fabrication factory and the sample concentrations of 234U and 238U were analyzed by α-spectrometry after radiochemical preparation using a TBP-based liquidliquid separation method. Personal air samplers (PAS) filters were also analyzed for determination of inhaled uranium activity.

    The results show that there is a large day-to-day variation (7-70 Bq d-1) of the inhaled 234U activity over a 6 week period. A large variation is also seen for the 234U activity concentration among 12 urine samples collected over a 12 week period; (2-50 mBq kg-1). Four hair samples from the same subject and period showed less variation (100-240 mBq g-1) as they reflect the average excretion over a longer period than the periodic urine samples.

    The total inhalation intake and excretion in urine and hair was obtained for two study subjects over a 6 week period. The uranium inhalation to urine and hair factors finh,u and finh,h were 0.0014 and 0.0002 respectively, given by calculations based on the measured PAS, urine and hair data. It has been demonstrated that scalp hair could be a valuable complement to urine as biomonitor of uranium intake.

  • 182.
    Ivarsson, Magnus
    et al.
    Swedish Museum Nat Hist, Sweden; Swedish Museum Nat Hist, Sweden.
    Broman, Curt
    Stockholm University, Sweden.
    Gustafsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Biomedical Engineering.
    Holm, Nils G.
    Stockholm University, Sweden.
    Biogenic Mn-Oxides in Subseafloor Basalts2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, p. e0128863-Article in journal (Refereed)
    Abstract [en]

    The deep biosphere of the subseafloor basalts is recognized as a major scientific frontier in disciplines like biology, geology, and oceanography. Recently, the presence of fungi in these environments has involved a change of view regarding diversity and ecology. Here, we describe fossilized fungal communities in vugs in subseafloor basalts from a depth of 936.65 metres below seafloor at the Detroit Seamount, Pacific Ocean. These fungal communities are closely associated with botryoidal Mn oxides composed of todorokite. Analyses of the Mn oxides by Electron Paramagnetic Resonance spectroscopy (EPR) indicate a biogenic signature. We suggest, based on mineralogical, morphological and EPR data, a biological origin of the botryoidal Mn oxides. Our results show that fungi are involved in Mn cycling at great depths in the seafloor and we introduce EPR as a means to easily identify biogenic Mn oxides in these environments.

    Download full text (pdf)
    fulltext
  • 183.
    Jackowski, Christian
    et al.
    University of Bern, Switzerland .
    Schwendener, Nicole
    University of Bern, Switzerland .
    Grabherr, Silke
    University of Lausanne, Switzerland .
    Persson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Post-Mortem Cardiac 3-T Magnetic Resonance Imaging Visualization of Sudden Cardiac Death?2013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 62, no 7, p. 617-629Article in journal (Refereed)
    Abstract [en]

    Objectives This study aimed to investigate post-mortem magnetic resonance imaging (pmMRI) for the assessment of myocardial infarction and hypointensities on post-mortem T-2-weighted images as a possible method for visualizing the myocardial origin of arrhythmic sudden cardiac death. less thanbrgreater than less thanbrgreater thanBackground Sudden cardiac death has challenged clinical and forensic pathologists for decades because verification on post-mortem autopsy is not possible. pmMRI as an autopsy-supporting examination technique has been shown to visualize different stages of myocardial infarction. less thanbrgreater than less thanbrgreater thanMethods In 136 human forensic corpses, a post-mortem cardiac MR examination was carried out prior to forensic autopsy. Short-axis and horizontal long-axis images were acquired in situ on a 3-T system. less thanbrgreater than less thanbrgreater thanResults In 76 cases, myocardial findings could be documented and correlated to the autopsy findings. Within these 76 study cases, a total of 124 myocardial lesions were detected on pmMRI (chronic: 25; subacute: 16; acute: 30; and peracute: 53). Chronic, subacute, and acute infarction cases correlated excellently to the myocardial findings on autopsy. Peracute infarctions (age range: minutes to approximately 1 h) were not visible on macroscopic autopsy or histological examination. Peracute infarction areas detected on pmMRI could be verified in targeted histological investigations in 62.3% of cases and could be related to a matching coronary finding in 84.9%. A total of 15.1% of peracute lesions on pmMRI lacked a matching coronary finding but presented with severe myocardial hypertrophy or cocaine intoxication facilitating a cardiac death without verifiable coronary stenosis. less thanbrgreater than less thanbrgreater thanConclusions 3-T pmMRI visualizes chronic, subacute, and acute myocardial infarction in situ. In peracute infarction as a possible cause of sudden cardiac death, it demonstrates affected myocardial areas not visible on autopsy. pmMRI should be considered as a feasible post-mortem investigation technique for the deceased patient if no consent for a clinical autopsy is obtained.

  • 184.
    Johansson, Mats
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Escobar Kvitting, John-Peder
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Flatebø, Torun
    Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway.
    Nicolaysen, Anne
    Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway.
    Nicolaysen, Gunnar
    Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Inhibition of constitutive nitric oxide synthase does not influence ventilation: matching in normal prone adult sheep with mechanical ventilation2016In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 123, no 6, p. 1492-1499Article in journal (Refereed)
    Abstract [en]

    Background

    Local formation of nitric oxide (NO) in the lung in proportion to ventilation, leading to vasodilation, is a putative mechanism behind ventilation- perfusion matching. We examined the role of local constitutive NO formation on regional distributions of ventilation (V) and perfusion (Q) and ventilation-perfusion matching (V/Q) in mechanically ventilated adult sheep with normal gas exchange.

    Methods

    V and Q were analyzed in lung regions (≈1.5 cm3) before and after inhibition of constitutive nitric oxide synthase (cNOS) with Nω-nitro-L-arginine methyl ester (L-NAME) (25 mg/kg) in seven prone sheep ventilated with PEEP. V and Q were measured using aerosolized fluorescent and infused radiolabeled microspheres, respectively. The animals were exsanguinated while deeply anaesthetized; lungs were excised, dried at total lung capacity and divided into cube units. The spatial location for each cube was tracked and fluorescence and radioactivity per unit weight determined.

    Results

    Pulmonary artery pressure increased significantly after L-NAME (from mean 16.6 to 23.6 mmHg, P<0.01) while there were no significant changes in PaO2, PaCO2 or SD log(V/Q). Distribution of V was not influenced by L-NAME but a small redistribution of Q from ventral to dorsal lung regions resulting in less heterogeneity in Q along the gravitational axis was seen (p<0.01). Perfusion to regions with the highest ventilation (5th quintile of the V distribution) remained unchanged with L-NAME.

    Conclusions

    There was minimal or no influence of cNOS inhibition by L-NAME on the distributions of V and Q, and V/Q in prone anesthetized and ventilated adult sheep with normal gas exchange.

  • 185.
    Jönsson, Daniel
    et al.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Bergström, Albin
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Algström, Isac
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Simon, Rozalyn
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hotz, Ingrid
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Visual Analysis for Understanding Irritable Bowel Syndrome2019In: Biomedical Visualisation / [ed] Paul Rea, Cham: Springer, 2019, p. 111-122Chapter in book (Refereed)
    Abstract [en]

    The cause of irritable bowel syndrome (IBS), a chronic disorder characterized by abdominal pain and disturbed bowel habits, is largely unknown. It is believed to be related to physical properties in the gut, central mechanisms in the brain, psychological factors, or a combination of these. To understand the relationships within the gut-brain axis with respect to IBS, large numbers of measurements ranging from stool samples to functional magnetic resonance imaging are collected from patients with IBS and healthy controls. As such, IBS is a typical example in medical research where research turns into a big data analysis challenge. In this chapter we demonstrate the power of interactive visual data analysis and exploration to generate an environment for scientific reasoning and hypothesis formulation for data from multiple sources with different character. Three case studies are presented to show the utility of the presented work.

  • 186.
    Jönsson, Daniel
    et al.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Science & Engineering.
    Bergström, Albin
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Forsell, Camilla
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Simon, Rozalyn
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ynnerman, Anders
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Science & Engineering.
    Hotz, Ingrid
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    A Visual Environment for Hypothesis Formation and Reasoning in Studies with fMRI and Multivariate Clinical Data2019In: Eurographics Workshop on Visual Computing for Biology and Medicine, 2019Conference paper (Refereed)
    Abstract [en]

    We present an interactive visual environment for linked analysis of brain imaging and clinical measurements. The environment is developed in an iterative participatory design process involving neuroscientists investigating the causes of brain-related complex diseases. The hypotheses formation process about correlations between active brain regions and physiological or psychological factors in studies with hundreds of subjects is a central part of the investigation. Observing the reasoning patterns during hypotheses formation, we concluded that while existing tools provide powerful analysis options, they lack effective interactive exploration, thus limiting the scientific scope and preventing extraction of knowledge from available data.Based on these observations, we designed methods that support neuroscientists by integrating their existing statistical analysis of multivariate subject data with interactive visual explorationto enable them to better understand differences between patient groups and the complex bidirectional interplay between clinical measurement and the brain. These exploration concepts enable neuroscientists, for the first time during their investigations, to interactively move between and reason about questions such as ‘which clinical measurements are correlated with a specific brain region?’ or ‘are there differences in brain activity between depressed young and old subjects?’. The environment uses parallel coordinates for effective overview and selection of subject groups, Welch's t-test to filter out brain regions with statistically significant differences, and multiple visualizations of Pearson correlations between brain regions and clinical parameters to facilitate correlation analysis. A qualitative user study was performed with three neuroscientists from different domains. The study shows that the developed environment supports simultaneous analysis of more parameters, provides rapid pathways to insights, and is an effective support tool for hypothesis formation.

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  • 187.
    Karageorgis, Anastassia
    et al.
    Safety and ADME Translational Sciences, Drug Safety and Metabolism, AstraZeneca, Gothenburg, Sweden..
    Lenhard, Stephen
    Bioimaging, Platform Technology and Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America..
    Yerby, Brittany
    Research Imaging Sciences, Amgen, Thousand Oaks, California, United States of America..
    Forsgren, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Wolfram MathCore, Linköping, Sweden.
    Liachenko, Serguei
    National Center for Toxicological Research, Division of Neurotoxicology, United States Food and Drug Administration, Jefferson, Arkansas, United States of America..
    Johansson, Edvin
    Personalised Healthcare and Biomarkers, Imaging group, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden..
    Pilling, Mark
    Biostatistics, Quantitative Biology, Discovery Sciences, Innovative Medicines and Early Development, AstraZeneca RandD, Cambridge, United Kingdom..
    Peterson, Richard
    Safety Assessment, GlaxoSmithKline, Research Triangle Park, Durham, North Carolina, United States of America..
    Yang, Xi
    National Center for Toxicological Research, Division of Systems Biology, United States Food and Drug Administration, Jefferson, Arkansas, United States of America..
    Williams, Dominic
    Safety and ADME Translational Sciences, Drug Safety and Metabolism, AstraZeneca, Cambridge, United Kingdom..
    Ungersma, Sharon
    Research Imaging Sciences, Amgen, Thousand Oaks, California, United States of America..
    Morgan, Ryan
    Department of Comparative Biology and Safety Sciences, Amgen Inc., Thousand Oaks, California, United States of America..
    Brouwer, Kim
    Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of N orth Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America..
    Jucker, Beat
    Bioimaging, Platform Technology and Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America..
    Hockings, Paul
    Antaros Medical, BioVenture Hub, Mölndal, Sweden.; MedTech West, Chalmers University of Technology, Gothenburg, Sweden..
    A multi-center preclinical study of gadoxetate DCE-MRI in rats as a biomarker of drug induced inhibition of liver transporter function.2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 5, article id e0197213Article in journal (Refereed)
    Abstract [en]

    Drug-induced liver injury (DILI) is a leading cause of acute liver failure and transplantation. DILI can be the result of impaired hepatobiliary transporters, with altered bile formation, flow, and subsequent cholestasis. We used gadoxetate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), combined with pharmacokinetic modelling, to measure hepatobiliary transporter function in vivo in rats. The sensitivity and robustness of the method was tested by evaluating the effect of a clinical dose of the antibiotic rifampicin in four different preclinical imaging centers. The mean gadoxetate uptake rate constant for the vehicle groups at all centers was 39.3 +/- 3.4 s-1 (n = 23) and 11.7 +/- 1.3 s-1 (n = 20) for the rifampicin groups. The mean gadoxetate efflux rate constant for the vehicle groups was 1.53 +/- 0.08 s-1 (n = 23) and for the rifampicin treated groups was 0.94 +/- 0.08 s-1 (n = 20). Both the uptake and excretion transporters of gadoxetate were statistically significantly inhibited by the clinical dose of rifampicin at all centers and the size of this treatment group effect was consistent across the centers. Gadoxetate is a clinically approved MRI contrast agent, so this method is readily transferable to the clinic.less thanbr /greater thanConclusion: Rate constants of gadoxetate uptake and excretion are sensitive and robust biomarkers to detect early changes in hepatobiliary transporter function in vivo in rats prior to established biomarkers of liver toxicity.

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  • 188.
    Kardell, Martin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Magnusson, Maria
    Linköping University, Department of Electrical Engineering, Computer Vision. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Faculty of Science & Engineering.
    Sandborg, Michael
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Alm Carlsson, Gudrun
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Jeuthe, Julius
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Malusek, Alexandr
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    AUTOMATIC SEGMENTATION OF PELVIS FOR BRACHYTHERAPYOF PROSTATE2016In: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 169, no 1-4, p. 398-404Article in journal (Refereed)
    Abstract [en]

    Advanced model-based iterative reconstruction algorithms in quantitative computed tomography (CT) perform automatic segmentation of tissues to estimate material properties of the imaged object. Compared with conventional methods, these algorithms may improve quality of reconstructed images and accuracy of radiation treatment planning. Automatic segmentation of tissues is, however, a difficult task. The aim of this work was to develop and evaluate an algorithm that automatically segments tissues in CT images of the male pelvis. The newly developed algorithm (MK2014) combines histogram matching, thresholding, region growing, deformable model and atlas-based registration techniques for the segmentation of bones, adipose tissue, prostate and muscles in CT images. Visual inspection of segmented images showed that the algorithm performed well for the five analysed images. The tissues were identified and outlined with accuracy sufficient for the dual-energy iterative reconstruction algorithm whose aim is to improve the accuracy of radiation treatment planning in brachytherapy of the prostate.

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  • 189.
    Karlsson, Anette
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Åslund, Ulrika
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    West, Janne
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). KTH Royal Institute Technology, Sweden.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Peolsson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    An Investigation of Fat Infiltration of the Multifidus Muscle in Patients With Severe Neck Symptoms Associated With Chronic Whiplash-Associated Disorder2016In: Journal of Orthopaedic and Sports Physical Therapy, ISSN 0190-6011, E-ISSN 1938-1344, Vol. 46, no 10, p. 886-893Article in journal (Refereed)
    Abstract [en]

    STUDY DESIGN: Cross-sectional study. BACKGROUND: Findings of fat infiltration in cervical spine multifidus, as a sign of degenerative morphometric changes due to whiplash injury, need to be verified. OBJECTIVES: To develop a method using water/fat magnetic resonance imaging (MRI) to investigate fat infiltration and cross-sectional area of multifidus muscle in individuals with whiplash associated disorders (WADS) compared to healthy controls. METHODS: Fat infiltration and cross-sectional area in the multifidus muscles spanning the C4 to C7 segmental levels were investigated by manual segmentation using water/fat-separated MRI in 31 participants with WAD and 31 controls, matched for age and sex. RESULTS: Based on average values for data spanning C4 to C7, participants with severe disability related to WAD had 38% greater muscular fat infiltration compared to healthy controls (P = .03) and 45% greater fat infiltration compared to those with mild to moderate disability related to WAD (P = .02). There were no significant differences between those with mild to moderate disability and healthy controls. No significant differences between groups were found for multifidus cross-sectional area. Significant differences were observed for both cross-sectional area and fat infiltration between segmental levels. CONCLUSION: Participants with severe disability after a whiplash injury had higher fat infiltration in the multifidus compared to controls and to those with mild/moderate disability secondary to WAD. Earlier reported findings using T1-weighted MRI were reproduced using refined imaging technology. The results of the study also indicate a risk when segmenting single cross-sectional slices, as both cross-sectional area and fat infiltration differ between cervical levels.

  • 190.
    Karlsson, Anette
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering.
    Linge, Jennifer
    Advanced MR Analytics AB.
    West, Janne
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Bell, Jimmy
    Westminster University, London, UK.
    Borga, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Defining Sarcopenia with MRI - Establishing Threshold Values within a Large-Scale Population Study2016Conference paper (Other academic)
    Abstract [en]

    PURPOSE

    To identify gender specific threshold values for sarcopenia detection for lean thigh muscle tissue volume quantified using MRI.

    METHOD AND MATERIALS

    Current gender-specific thresholds for sarcopenia detection are based on quantification on appendicular lean tissue normalized with height^2 using DXA (7.26 kg/m2 for men and 5.45 kg/m2 for women). In this study 3514 subjects (1548 males and 1966 females) in the imaging subcohort of UK Biobank with paired DXA and MRI scans were included. The age range was 45 to 78 years. The total lean thigh volume normalized with height2 (TTVi) was determined with a 6 minutes neck to knee 2-point Dixon MRI protocol using a 1.5T MR-scanner (Siemens, Germany) followed by analysis with AMRA® Profiler (AMRA, Sweden). The appendicular lean tissue mass normalized with height2 (ALTMi) was assessed using DXA (GE-Lunar iDXA). Subjects with ALTMi lower than the gender specific threshold were categorized as sarcopenic. Gender specific threshold values were determined for detection of sarcopenic subjects based on TTVi optimizing sensitivity and specificity. Area under receiver operator curve (AUROC) was calculated as well as the linear correlation between TTVi and ALTMi.

    RESULTS

    A threshold value of TTVi = 3.64 l/m2 provided a sensitivity and specificity of 0.88 for sarcopenia detection in males. The AUROC was 0.96. Similarly, a TTVi < 2.76 l/m2 identified sarcopenic female subjects with a sensitivity and specificity of 0.89. The corresponding AUROC was 0.96. The linear correlation between TTVi and ALTMi was 0.93 (99%CI: 0.93-0.94).

    CONCLUSION

    MRI-based quantification of total lean thigh volume normalized with height^2 could be used to categorize sarcopenia in the study group. Threshold values are suggested.

    CLINICAL RELEVANCE/APPLICATION

    The study suggests that sarcopenia can be diagnosed using a rapid MRI scan with high sensitivity and specificity.

  • 191.
    Karlsson, Anette
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Peolsson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Elliott, James
    The University of Sydney, Australia; Northwestern University, USA.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Science & Engineering.
    Ljunggren, Helena
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    The relation between local and distal muscle fat infiltration in chronic whiplash using magnetic resonance imaging.2019In: PLoS ONE, E-ISSN 1932-6203, Vol. 14, no 12, article id e0226037Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to investigate the relationship between fat infiltration in the cervical multifidi and fat infiltration measured in the lower extremities to move further into understanding the complex signs and symptoms arising from a whiplash trauma. Thirty-one individuals with chronic whiplash associated disorders, stratified into a mild/moderate group and a severe group, together with 31 age- and gender matched controls were enrolled in this study. Magnetic resonance imaging was used to acquire a 3D volume of the neck and of the whole-body. Cervical multifidi was used to represent muscles local to the whiplash trauma and all muscles below the hip joint, the lower extremities, were representing widespread muscles distal to the site of the trauma. The fat infiltration was determined by fat fraction in the segmented images. There was a linear correlation between local and distal muscle fat infiltration (p<0.001, r2 = 0.28). The correlation remained significant when adjusting for age and WAD group (p = 0.009) as well as when correcting for age, WAD group and BMI (p = 0.002). There was a correlation between local and distal muscle fat infiltration within the severe WAD group (p = 0.0016, r2 = 0.69) and in the healthy group (p = 0.022, r2 = 0.17) but not in the mild/moderate group (p = 0.29, r2 = 0.06). No significant differences (p = 0.11) in the lower extremities' MFI between the different groups were found. The absence of differences between the groups in terms of lower extremities' muscle fat infiltration indicates that, in this particular population, the whiplash trauma has a local effect on muscle fat infiltration rather than a generalized.

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  • 192.
    Karlsson, Anette
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Rosander, Johannes
    Advanced MR Analytics AB, Linköping, Sweden.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tallberg, Joakim
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Grönqvist, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Automatic and quantitative assessment of regional muscle volume by multi-atlas segmentation using whole-body water–fat MRI2015In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 41, no 6, p. 1558-1569Article in journal (Refereed)
    Abstract [en]

    Purpose

    To develop and demonstrate a rapid whole-body magnetic resonance imaging (MRI) method for automatic quantification of total and regional skeletal muscle volume.

    Materials and Methods

    The method was based on a multi-atlas segmentation of intensity corrected water–fat separated image volumes. Automatic lean muscle tissue segmentations were achieved by nonrigid registration of atlas datasets with 10 different manually segmented muscle groups. Ten subjects scanned at 1.5 T and 3.0 T were used as atlases, initial validation and optimization. Further validation used 11 subjects scanned at 3.0 T. The automated and manual segmentations were compared using intraclass correlation, true positive volume fractions, and delta volumes.

    Results

    For the 1.5 T datasets, the intraclass correlation, true positive volume fractions (mean ± standard deviation, SD), and delta volumes (mean ± SD) were 0.99, 0.91 ± 0.02, −0.10 ± 0.70L (whole body), 0.99, 0.93 ± 0.02, 0.01 ± 0.07L (left anterior thigh), and 0.98, 0.80 ± 0.07, −0.08 ± 0.15L (left abdomen). The corresponding values at 3.0 T were 0.97, 0.92 ± 0.03, −0.17 ± 1.37L (whole body), 0.99, 0.93 ± 0.03, 0.03 ± 0.08L (left anterior thigh), and 0.89, 0.90 ± 0.04, −0.03 ± 0.42L (left abdomen). The validation datasets showed similar results.

    Conclusion

    The method accurately quantified the whole-body skeletal muscle volume and the volume of separate muscle groups independent of field strength and image resolution. 

  • 193.
    Karlsson, Anette
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Rosander, Johannes
    Advanced MR Analytics AB, Linköping, Sweden.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tallberg, Joakim
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Grönqvist, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Automatic and Quantitative Assessment of Total and Regional Muscle Tissue Volume using Multi-Atlas Segmentation2014Conference paper (Other academic)
    Abstract [en]

    Accurate and precise assessment of human muscle tissue is important for further understanding of different muscle diseases and syndromes. We present a rapid whole body MR method for automatic quantification of total and regional muscle volume. The method is based on multi-atlas segmentation of intensity corrected water-fat separated images. The method was validated with a leave-one-out approach, using manually segmented atlases from 10 subjects as ground truth. The result gave a coefficient of variation on total muscle volume equal to 1.25±1.35 % (mean ± standard deviation). The method enables cost-efficient large-scale studies, investigating conditions such as sarcopenia and muscular dystrophies.

  • 194.
    Karlsson, Anette
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Rosander, Johannes
    Advanced MR Analytics AB, Linköping, Sweden.
    Tallberg, Joakim
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Grönqvist, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Automatic and Quantitative Assessment of Total and Regional Muscle Tissue Volume using Multi-Atlas Segmentation2015In: International Society for Magnetic Resonance in Medicince Annual Meeting: Proceedings, 2015Conference paper (Other academic)
    Abstract [en]

    The purpose is to develop and demonstrate a rapid whole-body MRI method for automatic quantification of total and regional lean skeletal muscle volume. Quantitative water and fat separated image volumes of the whole body are manually segmented and used as atlases. The atlases are non-rigidly registered onto to a new image volume and the muscle groups are classified using a voting scheme. A leave-one-out approach with subjects scanned in a 1.5 T and a 3.0 T scanner is used for validation. The method quantifies the whole-body skeletal muscle volumes and the volumes of separate muscle groups independently of image resolution.

  • 195.
    Karlsson, Anette
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Rosander, Johannes
    Tallberg, Joakim
    Romu, Thobias
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Borga, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Whole Body Muscle Classification using Multiple Prototype Voting2013Conference paper (Other academic)
  • 196.
    Karlsson, Louise
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Andersson, Mikael
    National Board Forens Med, Department Forens Genet and Forens Toxicol, SE-58758 Linkoping, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Kugelberg, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Mephedrone, Methylone and 3,4-Methylenedioxypyrovalerone (MDPV) Induce Conditioned Place Preference in Mice2014In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 115, no 5, p. 411-416Article in journal (Refereed)
    Abstract [en]

    During the last decade, there has been a worldwide increase in popularity and abuse of synthetic cathinones. Common ingredients of the so-called bath salts include mephedrone, methylone and 3,4-methylenedioxypyrovalerone (MDPV). Relatively little information about the pharmacology and addiction potential of these drugs is available. We used the conditioned place preference (CPP) paradigm to explore the reinforcing effects of three different synthetic cathinones. The primary aim of this study was to investigate whether mephedrone, methylone and MDPV induce CPP in mice. The secondary aims were to investigate a possible dose-response CPP and whether the synthetic cathinones induce higher CPP than amphetamine at equal dose. C57BL/6 mice were conditioned to mephedrone, methylone, MDPV and amphetamine at doses of 0.5, 2, 5, 10 or 20mg/kg (i.p.). During the conditioning, the mice received two training sessions per day for 4days. All four tested drugs showed a significant place preference compared with controls. Mice conditioned with MDPV (5 and 10mg/kg) displayed a greater preference score compared to mice conditioned with amphetamine (5 and 10mg/kg). Our findings show that mephedrone, methylone and MDPV produce CPP equal or higher than amphetamine strongly suggesting addictive properties. Given the public health concern of abuse, future pharmacological studies are necessary to fully understand the effects of these drugs.

  • 197. Order onlineBuy this publication >>
    Karlsson, Markus
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Non-Invasive Characterization of Liver Disease: By Multimodal Quantitative Magnetic Resonance2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    There is a large and unmet need for diagnostic tool that can be used to characterize chronic liver diseases (CLD). In the earlier stages of CLD, much of the diagnostics involves performing biopsies, which are evaluated by a histopathologist for the presence of e.g. fat, iron, inflammation, and fibrosis. Performing biopsies, however, have two downsides: i) biopsies are invasive and carries a small but non-negligible risk for serious complications, ii) biopsies only represents a tiny portion of the liver and are thus prone to sampling error. Moreover, in the later stages of CLD, when the disease has progressed far enough, the ability of the liver to perform its basic function will be compromised. In this stage, there is a need for better methods for accurately measuring liver function. Additionally, measures of liver function can also be used when developing new drugs, as biomarkers for drug-induced liver injury (DILI), which is a serious drug-safety issue.

    Magnetic resonance imaging (MRI) is a non-invasive medical imaging modality, which have shown much promise with regards to characterizing liver disease in all of the abovementioned aspects. The aim of this PhD project was to develop and validate MR-based methods that can be used to non-invasively characterize liver disease.

    Paper I investigated if R2* mapping, a MR-method for measuring liver iron content, can be confounded by liver fat. The results show fat does affect R2*. The conclusion was therefore that fat must be taken into account when measuring small amounts of liver iron, as a small increase in R2* could be due to either small amounts of iron or large amounts of fat.

    Paper II examined whether T1 mapping, which is another MR-method, can be used for staging liver fibrosis. The results of previous research have been mixed; some studies have been very promising, whereas other studies have been less promising. Unfortunately, the results in Paper II belongs to the less promising studies.

    Paper III focused on measuring liver function by dynamic contrast-enhanced MRI (DCEMRI) using a liver specific contrast agent, which is taken up the hepatocytes and excreted to the bile. The purpose of the paper was to extend and validate a method for estimating uptake and efflux rates of the contrast agent. The method had previously only been applied in health volunteers. Paper II showed that the method can be applied to CLD patients and that the uptake of the contrast agent is lower in patients with advanced fibrosis.

    Paper IV also used studied liver function with DCE-MRI in patients with primary sclerosing cholangitis (PSC). PSC is a CLD where the bile ducts are attacked by the immune system. When diagnosing PSC patients, it is common to use magnetic resonance cholangiopancreatography (MRCP), which is a method for imaging the bile ducts. Paper IV examined if there was any correlation between number and severity of the morphological changes, seen on MRCP, and measures of liver function derived using DCE-MRI. However, the results showed no such correlation. The conclusion was that the results indicates that MRCP should not be used to predict parenchymal function.

    Paper V developed a method for translating DCE-MRI liver function parameters from rats to humans. This translation could be of value when developing new drugs, as a tool for predicting which drugs might cause drug-induced liver injury.

    In summary, this thesis has shown that multimodal quantitative MR has a bright future for characterizing liver disease from a range of different aspects.

    List of papers
    1. Liver R2*is affected by both iron and fat: A dual biopsy-validated study of chronic liver disease
    Open this publication in new window or tab >>Liver R2*is affected by both iron and fat: A dual biopsy-validated study of chronic liver disease
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    2019 (English)In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 50, no 1, p. 325-333Article in journal (Refereed) Published
    Abstract [en]

    Background Liver iron content (LIC) in chronic liver disease (CLD) is currently determined by performing an invasive liver biopsy. MRI using R2* relaxometry is a noninvasive alternative for estimating LIC. Fat accumulation in the liver, or proton density fat fraction (PDFF), may be a possible confounder of R2* measurements. Previous studies of the effect of PDFF on R2* have not used quantitative LIC measurement. Purpose To assess the associations between R2*, LIC, PDFF, and liver histology in patients with suspected CLD. Study Type Prospective. Population Eighty-one patients with suspected CLD. Field Strength/Sequence 1.5 T. Multiecho turbo field echo to quantify R2*. PRESS MRS to quantify PDFF. Assessment Each patient underwent an MR examination, followed by two needle biopsies immediately following the MR examination. The first biopsy was used for conventional histological assessment of LIC, whereas the second biopsy was used to quantitatively measure LIC using mass spectrometry. R2* was correlated with both LIC and PDFF. A correction for the influence of fat on R2* was calculated. Statistical Tests Pearson correlation, linear regression, and area under the receiver operating curve. Results There was a positive linear correlation between R2* and PDFF (R = 0.69), after removing data from patients with elevated iron levels, as defined by LIC. R2*, corrected for PDFF, was the best method for identifying patients with elevated iron levels, with a correlation of R = 0.87 and a sensitivity and specificity of 87.5% and 98.6%, respectively. Data Conclusion PDFF increases R2*. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:325-333.

    Place, publisher, year, edition, pages
    WILEY, 2019
    Keywords
    liver iron content; liver fat; R2*; PDFF; iron overload
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:liu:diva-158842 (URN)10.1002/jmri.26601 (DOI)000471831600033 ()30637926 (PubMedID)
    Note

    Funding Agencies|Region Ostergotland; Medical Research council of Southeast Sweden [FORSS #12621]; Swedish Research Council [VR/NT #2014-6157, VR/MH, #2007-2884]; Forskningsradet i Sydostra Sverige; Linkoping University; Linkoping University Hospital Research Foundations; Vinnova [#2013-01314]; Vetenskapsradet

    Available from: 2019-07-15 Created: 2019-07-15 Last updated: 2019-12-12
    2. Model-inferred mechanisms of liver function from magnetic resonance imaging data: Validation and variation across a clinically relevant cohort
    Open this publication in new window or tab >>Model-inferred mechanisms of liver function from magnetic resonance imaging data: Validation and variation across a clinically relevant cohort
    Show others...
    2019 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 15, no 6, article id e1007157Article in journal (Refereed) Published
    Abstract [en]

    Estimation of liver function is important to monitor progression of chronic liver disease (CLD). A promising method is magnetic resonance imaging (MRI) combined with gadoxetate, a liver-specific contrast agent. For this method, we have previously developed a model for an average healthy human. Herein, we extended this model, by combining it with a patient-specific non-linear mixed-effects modeling framework. We validated the model by recruiting 100 patients with CLD of varying severity and etiologies. The model explained all MRI data and adequately predicted both timepoints saved for validation and gadoxetate concentrations in both plasma and biopsies. The validated model provides a new and deeper look into how the mechanisms of liver function vary across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate. These mechanisms are shared across many liver functions and can now be estimated from standard clinical images.

    Author summary

    Being able to accurately and reliably estimate liver function is important when monitoring the progression of patients with liver disease, as well as when identifying drug-induced liver injury during drug development. A promising method for quantifying liver function is to use magnetic resonance imaging combined with gadoxetate. Gadoxetate is a liver-specific contrast agent, which is taken up by the hepatocytes and excreted into the bile. We have previously developed a mechanistic model for gadoxetate dynamics using averaged data from healthy volunteers. In this work, we extended our model with a non-linear mixed-effects modeling framework to give patient-specific estimates of the gadoxetate transport-rates. We validated the model by recruiting 100 patients with liver disease, covering a range of severity and etiologies. All patients underwent an MRI-examination and provided both blood and liver biopsies. Our validated model provides a new and deeper look into how the mechanisms of liver function varies across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate.

    Place, publisher, year, edition, pages
    San Francisco, CA, United States: Public Library of Science, 2019
    National Category
    Pharmaceutical Sciences
    Identifiers
    urn:nbn:se:liu:diva-159165 (URN)10.1371/journal.pcbi.1007157 (DOI)000474703000068 ()31237870 (PubMedID)2-s2.0-85069296906 (Scopus ID)
    Note

    Funding Agencies|Swedish Research Council [2014-6157, 2007-2884]; Medical Research council of Southeast Sweden [12621]; Vinnova [2013-01314]; Linkoping University, CENIIT [15.09]; Swedish fund for research without animal experiments [Nytank2015]

    Available from: 2019-07-30 Created: 2019-07-30 Last updated: 2019-12-12Bibliographically approved
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  • 198.
    Karlsson, Markus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ekstedt, Mattias
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Dahlström, Nils
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Forsgren, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Norén, Bengt
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Liver R2*is affected by both iron and fat: A dual biopsy-validated study of chronic liver disease2019In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 50, no 1, p. 325-333Article in journal (Refereed)
    Abstract [en]

    Background Liver iron content (LIC) in chronic liver disease (CLD) is currently determined by performing an invasive liver biopsy. MRI using R2* relaxometry is a noninvasive alternative for estimating LIC. Fat accumulation in the liver, or proton density fat fraction (PDFF), may be a possible confounder of R2* measurements. Previous studies of the effect of PDFF on R2* have not used quantitative LIC measurement. Purpose To assess the associations between R2*, LIC, PDFF, and liver histology in patients with suspected CLD. Study Type Prospective. Population Eighty-one patients with suspected CLD. Field Strength/Sequence 1.5 T. Multiecho turbo field echo to quantify R2*. PRESS MRS to quantify PDFF. Assessment Each patient underwent an MR examination, followed by two needle biopsies immediately following the MR examination. The first biopsy was used for conventional histological assessment of LIC, whereas the second biopsy was used to quantitatively measure LIC using mass spectrometry. R2* was correlated with both LIC and PDFF. A correction for the influence of fat on R2* was calculated. Statistical Tests Pearson correlation, linear regression, and area under the receiver operating curve. Results There was a positive linear correlation between R2* and PDFF (R = 0.69), after removing data from patients with elevated iron levels, as defined by LIC. R2*, corrected for PDFF, was the best method for identifying patients with elevated iron levels, with a correlation of R = 0.87 and a sensitivity and specificity of 87.5% and 98.6%, respectively. Data Conclusion PDFF increases R2*. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:325-333.

    The full text will be freely available from 2020-09-13 14:26
  • 199.
    Karlsson, Markus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Forsgren, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Dahlström, Nils
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Leinhard Dahlqvist, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Norén, Bengt
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Ekstedt, Mattias
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Diffuse Liver Disease: Measurements of Liver Trace Metal Concentrations and R2* Relaxation Rates2016Conference paper (Refereed)
    Abstract [en]

    Introduction

    Over the past decade, several methods for measuring of liver iron content (LIC) non-invasively with MRI have been developed and verified. The most promising methods uses relaxometry, measuring either R2- or R2* relaxation rate in the liver1,2. For instance, several studies have shown that there seems to be a linear relationship between R2* and LIC1. However, few of these studies have measured the liver content of other metals, which could also affect the relaxation rates. The goal of this study was to investigate if any trace metals, other than iron could affect the R2* relaxation rate in liver tissue in a patients with diffuse liver disease.

    Subjects and methods

    75 patients with suspected diffuse liver disease underwent an MRI examination followed by a liver biopsy the same day. The R2* relaxation rate of the water protons in the liver was measured using an axial 3D multi-slice fat-saturated multi-echo turbo field echo sequence (TE=4.60/9.20/13.80/18.40/23.00ms). Regions of interest (ROI) were drawn and R2* was estimated by fitting the mean signal intensity from the ROIs to a mono-exponential decay model. The biopsies were freeze dried and the concentrations of iron, manganese, copper, cobalt and gadolinium were measured using Inductively Coupled Plasma Sector Field Mass Spectrometry (ICP-SFMS). A multiple linear regression analysis was applied to determine which of the measured metals significantly affected the relaxation rate.

    Results

    A linear regression with the LIC and R2* showed a reasonable fit (Figure 1). The multiple linear regression analysis (Table 1) showed that iron as well as manganese had a significant affect on R2*. Unlike iron however, the regression coefficient of manganese was negative, meaning that an increasing manganese concentration gave a shorter R2* relaxation rate. The same trend can be seen when plotting the manganese concentration against R2* (Figure 2).

  • 200.
    Karlsson, Mattias
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Nilsson, Josef
    Karolinska University Hospital, Sweden.
    Lundell, Marie
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Monte Carlo dosimetry of the eye plaque design used at the St. Erik Eye Hospital for I-125 brachytherapy2014In: Brachytherapy, ISSN 1538-4721, E-ISSN 1873-1449, Vol. 13, no 6, p. 651-656Article in journal (Refereed)
    Abstract [en]

    PURPOSE: At St. Erik Eye Hospital in Stockholm, Sweden, ocular tumors of apical height above 6 mm are treated with brachytherapy, using iodine-125 seeds attached to a gold alloy plaque while the treatment planning is performed assuming homogeneous water surroundings. The aim of this work was to investigate the dose-modifying effects of the plaque and the seed fixating silicone rubber glue. METHODS AND MATERIALS: The impact of the gold plaque and silicone rubber glue was studied with the Monte Carlo N-particle transport code, version 5. RESULTS: For the 2 cm most proximal to the plaque surface along the plaques central axis, the eyeball received 104.6-93.0% of the dose in all-water conditions. CONCLUSIONS: The 0.3 mm thick layer of silicone rubber glue, used for seed fixation, attenuates photons little enough to allow characteristic X-rays from the gold alloy plaque to reach the eyeball. Close to the plaque, the dose rates were higher with the plaque and glue present, than in homogeneous water conditions. This is in contrast to what has been reported for more commonly used eye plaques, demonstrating the importance of investigating the dosimetry of individual treatment systems.

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