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  • 1.
    Abdul Qadhr, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Suurküla, Madis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Whole-body diffusion-weighted imaging compared with FDG-PET/CT in staging of lymphoma patients2011In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 52, no 2, p. 173-180Article in journal (Refereed)
    Abstract [en]

    Background:

    Diffusion-weighted imaging (DWI) has become increasingly valuable in lymph node imaging, yet the clinical utility of this technique in the staging of lymphoma has not been established.

    Purpose:

    To compare whole-body DWI with FDG-PET/CT in the staging of lymphoma patients.

    Material and Methods:

    Thirty-one patients, eight with Hodgkin lymphoma (HL) and 23 with non-Hodgkin's lymphoma (18 aggressive and five indolent) underwent both whole-body DWI, whole-body MRI (T1W and T2W-STIR) and FDG-PET/CT. Lesions on whole-body DWI were only considered positive if they correlated with lesions on T1W and T2W-STIR images. The staging given by each technique was compared, according to the Ann Arbor staging system. Differences in staging were solved using biopsy results, and clinical and CT follow-ups as standard of reference.

    Results:

    The staging was the same for DWI and FDG-PET/CT in 28 (90.3%) patients and different in three (9.7%). Of the 28 patients with the same staging, 11 had stage IV in both techniques and 17 had stages 0-III. No HL or aggressive non-Hodgkin's lymphoma patients had different staging. Three indolent small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) lymphoma had higher staging with DWI when compared with FDG-PET/CT. One small subcutaneous breast lymphoma was not seen but all other extranodal sites were detected by both techniques.

    Conclusion:

    Whole-body DWI is a promising technique for staging of both (aggressive and indolent) non-Hodgkin's lymphoma and HL.

  • 2.
    Abdulla, Maysaa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Guglielmo, Priscilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Brotzu General Hospital, Cagliari, Italy.
    Hollander, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Prognostic impact of abdominal lymph node involvement in diffuse large B-cell lymphoma2020In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 104, no 3, p. 207-213Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The prognostic value of site of nodal involvement in diffuse large B-cell lymphomas (DLBCL) is mainly unknown. We aimed to determine the prognostic significance of nodal abdominal involvement in relation to tumour cell markers and clinical characteristics of 249 DLBCL patients in a retrospective single-centre study.

    METHODS: Contrast-enhanced computed tomography (CT) of the abdomen and thorax revealed pathologically enlarged abdominal lymph nodes in 156 patients, while in 93 patients there were no pathologically enlarged lymph nodes in the abdomen. In 81 cases, the diagnosis of DLBCL was verified by histopathological biopsy obtained from abdominal lymph node.

    RESULTS: Patients with abdominal nodal disease had inferior lymphoma-specific survival (P = .04) and presented with higher age-adjusted IPI (P < .001), lactate dehydrogenase (P < .001) and more often advanced stage (P < .001), bulky disease (P < .001), B symptoms (P < .001), and double expression of MYC and BCL2 (P = .02) compared to patients without nodal abdominal involvement, but less often extranodal involvement (P < .02). The worst outcome was observed in those where the abdominal nodal involvement was verified by histopathological biopsy.

    CONCLUSION: Diffuse large B-cell lymphomas patients with abdominal nodal disease had inferior outcome and more aggressive behaviour, reflected both in clinical and biological characteristics.

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  • 3.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    MultiHance in body MR angiography: personal experiences2004In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 14 Suppl 7, p. O52-O54Article in journal (Refereed)
  • 4.
    Ahlström, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ekström, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sjöholm, Therese
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, E.
    Antaros Med, Molndal, Sweden..
    Hagmar, P.
    Antaros Med, Molndal, Sweden..
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Registration-based automated lesion detection and therapy evaluation of tumors in whole body PET-MR images2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, no S5, article id 78PArticle in journal (Other academic)
  • 5.
    Ahmad, Nouman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Sparresäter, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Tarai, Sambit
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lundström, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bergström, Göran
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Automatic segmentation of large-scale CT image datasets for detailed body composition analysis.2023In: BMC Bioinformatics, E-ISSN 1471-2105, Vol. 24, no 1, article id 346Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Body composition (BC) is an important factor in determining the risk of type 2-diabetes and cardiovascular disease. Computed tomography (CT) is a useful imaging technique for studying BC, however manual segmentation of CT images is time-consuming and subjective. The purpose of this study is to develop and evaluate fully automated segmentation techniques applicable to a 3-slice CT imaging protocol, consisting of single slices at the level of the liver, abdomen, and thigh, allowing detailed analysis of numerous tissues and organs.

    METHODS: The study used more than 4000 CT subjects acquired from the large-scale SCAPIS and IGT cohort to train and evaluate four convolutional neural network based architectures: ResUNET, UNET++, Ghost-UNET, and the proposed Ghost-UNET++. The segmentation techniques were developed and evaluated for automated segmentation of the liver, spleen, skeletal muscle, bone marrow, cortical bone, and various adipose tissue depots, including visceral (VAT), intraperitoneal (IPAT), retroperitoneal (RPAT), subcutaneous (SAT), deep (DSAT), and superficial SAT (SSAT), as well as intermuscular adipose tissue (IMAT). The models were trained and validated for each target using tenfold cross-validation and test sets.

    RESULTS: The Dice scores on cross validation in SCAPIS were: ResUNET 0.964 (0.909-0.996), UNET++ 0.981 (0.927-0.996), Ghost-UNET 0.961 (0.904-0.991), and Ghost-UNET++ 0.968 (0.910-0.994). All four models showed relatively strong results, however UNET++ had the best performance overall. Ghost-UNET++ performed competitively compared to UNET++ and showed a more computationally efficient approach.

    CONCLUSION: Fully automated segmentation techniques can be successfully applied to a 3-slice CT imaging protocol to analyze multiple tissues and organs related to BC. The overall best performance was achieved by UNET++, against which Ghost-UNET++ showed competitive results based on a more computationally efficient approach. The use of fully automated segmentation methods can reduce analysis time and provide objective results in large-scale studies of BC.

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  • 6.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carrasquilla, Germán
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Langner, Taro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Menzel, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Censin, Jenny C.
    Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK; 7Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
    Sayols-Baixeras, Sergi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nguyen, Diem
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Mora, Andrés Martínez
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W.
    Clinical Diabetes and Metabolism, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Genetics of liver fat and volume associate with altered metabolism and whole body magnetic resonance imaging2022In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 77, p. S40-S40Article in journal (Other academic)
  • 7.
    Alsaqal, Salem
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hockings, Paul
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, Mölndal, Sweden.
    Gummesson, Anders
    Hedström, Anders
    Hulthe, Johannes
    Johansson, Lars
    Niessen, Heiko G
    Schoelch, Corinna
    Schultheis, Christian
    Vessby, Johan
    Wanders, Alkwin
    Rorsman, Fredrik
    Ebeling Barbier, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    The Combination of MR Elastography and Proton Density Fat Fraction Improves Diagnosis of Nonalcoholic Steatohepatitis.2022In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 56, no 2, p. -379Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide. It is subdivided into nonalcoholic fatty liver (NAFL) and the more aggressive form, nonalcoholic steatohepatitis (NASH), which carries a higher risk of developing fibrosis and cirrhosis. There is currently no reliable non-invasive method for differentiating NASH from NAFL.

    PURPOSE: To investigate the ability of magnetic resonance imaging (MRI)-based imaging biomarkers to diagnose NASH and moderate fibrosis as well as assess their repeatability.

    STUDY TYPE: Prospective.

    SUBJECTS: Sixty-eight participants (41% women) with biopsy-proven NAFLD (53 NASH and 15 NAFL). Thirty participants underwent a second MRI in order to assess repeatability.

    FIELD STRENGTH/SEQUENCE: 3.0 T; MR elastography (MRE) (a spin-echo echo-planar imaging [SE-EPI] sequence with motion-encoding gradients), MR proton density fat fraction (PDFF) and R2* mapping (a multi-echo three-dimensional gradient-echo sequence), T1 mapping (a single-point saturation-recovery technique), and diffusion-weighted imaging (SE-EPI sequence).

    ASSESSMENT: Quantitative MRI measurements were obtained and assessed alone and in combination with biochemical markers (cytokeratin-18 [CK18] M30, alanine transaminase [ALT], and aspartate transaminase [AST]) using logistic regression models. Models that could differentiate between NASH and NAFL and between moderate to advanced fibrosis (F2-4) and no or mild fibrosis (F0-1), based on the histopathological results, were identified.

    STATISTICAL TESTS: Independent samples t-test, Pearson's chi-squared test, area under the receiver operating characteristic curve (AUROC), Spearman's correlation, intra-individual coefficient of variation, and intraclass correlation coefficient (ICC). Statistical significance was set at P < 0.05.

    RESULTS: There was a significant difference between the NASH and NAFL groups with liver stiffness assessed with MRE, CK18 M30, and ALT, with an AUROC of 0.74, 0.76, and 0.70, respectively. Both MRE and PDFF contributed significantly to a bivariate model for diagnosing NASH (AUROC = 0.84). MRE could significantly differentiate between F2-4 and F0-1 (AUROC = 0.74). A model combining MRE with AST improved the diagnosis of F2-4 (AUROC = 0.83). The ICC for repeatability was 0.94 and 0.99 for MRE and PDFF, respectively.

    DATA CONCLUSION: MRE can potentially diagnose NASH and differentiate between fibrosis stages. Combining MRE with PDFF improves the diagnosis of NASH.

    LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

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  • 8.
    Amini, Hashem
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Second trimester fetal magnetic resonance imaging improves diagnosis of non-central nervous system anomalies2011In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 90, no 4, p. 380-389Article in journal (Refereed)
    Abstract [en]

    Objectives. To evaluate the additional information of second trimester magnetic resonance imaging (MRI) compared to ultrasound in fetuses with identified or suspected non-CNS anomalies and to study the clinical impact of the MRI information on pregnancy management. Design. Prospective study during 2003-2007. The fetal MRI examination was planned to be performed within three days after the ultrasound. Setting. Uppsala University hospital. Material and methods. Sixty-three women, where the second trimester ultrasound identified or raised suspicion of fetal anomalies were included. Ultrasound was compared to MRI in relation to the final diagnosis, which was based on the assessment of all available data including post-partum clinical follow-up and autopsy results. Main outcome measures. Evaluation of the additional information gained from MRI and the consequences it had on pregnancy management. Results. The mean interval between ultrasound and MRI was 2.6 days (range 0-15). In 42 (67%) cases MRI was performed within three days. All MRI examinations were assessable. In 43 (68%) fetuses MRI provided no additional information, in 17 (27%) MRI added information without changing the management and in three (5%) MRI provided additional information which changed the management. All these three cases had oligohydramnios. In all six cases of diaphragmatic hernia MRI provided additional information. Conclusions. Fetal MRI of non-CNS anomalies in the second trimester seems to be a valuable adjunct to ultrasound diagnosis of non-CNS anomalies, especially in cases of oligohydramnios and diaphragmatic hernia.

  • 9.
    Andersson, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Silvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikehult, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Patient Experience of an 18F-FDG-PET/CT Examination:: Need for Improvements in Patient Care2015In: Journal of Radiology Nursing, ISSN 1546-0843, Vol. 34, no 2, p. 100-108Article in journal (Refereed)
    Abstract [en]

    The aims of this study were to investigate the patients' knowledge about and experience of an 18F-fluoro-deoxy-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) examination and to investigate the self-reported feelings of stress, level of physical activity, and health-related quality of life (HRQoL) and to find out if this was related to how they experienced the examination. A cross-sectional survey was used to collect information on 198 patients with known or suspected malignancy. As many as 32% to 63% were satisfied with the nursing staff, the communication, and the professional skills. Most patients did not know beforehand what an FDG-PET/CT examination was. The HRQoL, level of perceived stress, and physical activity were relatively low. A better HRQoL, lower level of perceived stress, and a higher level of physical activity were correlated to a more positive experience and higher education to more knowledge about the examination (p < .01–.05). The information before the examination needs to be improved. The results may be used to improve patient care and optimize imaging procedures.

  • 10.
    Andersson, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Silvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Assessment of Whether Patients' Knowledge, Satisfaction, and Experience Regarding Their 18F-Fluoride PET/CT Examination Affects Image Quality2016In: Journal of Nuclear Medicine Technology, ISSN 0091-4916, E-ISSN 1535-5675, Vol. 44, no 1, p. 21-25Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate patients’ previous knowledge, satisfaction and experience regarding a (18F)-fluoride positron emission tomography / computed tomography examination ((18F)-fluoride PET/CT) and to explore whether experienced discomfort during the examination or pain was associated with reduced image quality. A further aim was to explore whether patients’ health-related quality of life (HRQoL) was associated with their satisfaction and experiences of the examination.

    Methods: Fifty consecutive patients with a histopathological diagnosis of prostate cancer who were scheduled for (18F)-fluoride PET/CT were asked to participate in the study, which was performed between November 2011 and April 2013. A questionnaire was used to collect information regarding the patients’ previous knowledge and experience of the examination. Image quality assessment was performed according to an arbitrary scale. The EORTC-QLQ-C30 and QLQ-PR25 were used to assess HRQoL.

    Results: Forty-six patients (96%) completed the questionnaires. Twenty-six per cent of participants did not know at all what a (18F)-fluoride PET/CT examination was. The majority (52-70%) were to a very high degree satisfied with the care provided by the nursing staff but less satisfied with the information given prior to the examination. The image quality was similar in patients who were exhausted or claustrophobic during the examination and those who were not. No correlations between HRQoL and the participants’ experience of (18F)-fluoride PET/CT were found.

    Conclusion: The majority of participants were satisfied with the care provided by the nursing staff, but there is still room for improvement especially regarding the information prior to the examination. Long examination time may be strenuous, for the patient but there was no difference in image quality between patients who felt discomfort during the examination or pain and those who did not.

  • 11.
    Andersson, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Trampal Pulido, Carlos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Effects of web-based information on patient satisfaction and image quality in patients undergoing an 18F-FDG PET/CT examination: a randomized controlled trial2018In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, no Suppl 1, p. S783-S784Article in journal (Other academic)
  • 12.
    Andersson, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Trampal Pulido, Carlos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Randomized Controlled Trial Examining Effects of Web-Based Information on Patient Satisfaction and Image Quality in 18F-FDG PET/CT Examinations2019In: Journal of Nuclear Medicine Technology, ISSN 0091-4916, E-ISSN 1535-5675, no 1, p. 36-46Article in journal (Refereed)
    Abstract [en]

    Our aim was to compare the effect that having access, versus not having access, to web-based patient information on 18F-FDG PET/CT has on image quality and on patient satisfaction with their care during and knowledge about the examination, as well as to explore whether patients utilized and were satisfied with the web-based information.

    Methods: We recruited 148 patients between October 2015 and December 2016 and randomly assigned them to a standard-care group or an intervention group. Both groups received standard information about the 18F-FDG PET/CT examination, but the intervention group also received access to web-based information. A questionnaire was used to evaluate patient satisfaction with, knowledge about, and discomfort during the examination, and a masked assessment of image quality was conducted.

    Results: Overall satisfaction was high in both groups. The lowest satisfaction was with information about how the patients would receive the results of the examination. More patients in the intervention group than in the standard-care group knew how the 18F-FDG PET/CT examination would be conducted. Descriptive data suggest that image quality was slightly better in the intervention group than in the standard-care group, but none of the outcomes significantly differed between the groups. However, several obstacles were encountered during recruitment that led to insufficient power to detect differences. Also, only 54 of 75 patients (72%) in the intervention group utilized the web-based information. However, those who did utilize the information were satisfied with it and found it helpful.

    Conclusion: The effects of web-based information need to be investigated in a larger sample of patients. Having access to improved information before undergoing 18F-FDG PET/CT may help patients prepare for and undergo the examination. It may also improve image quality. However, this possibility needs to be investigated using image quality as the primary outcome. The results may be used to improve patient information and care and thereby optimize the 18F-FDG PET/CT procedure.

  • 13.
    Andersson, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Johansson, Silvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikehult, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    18F-Fluorid-PET-CT: Patient expectations and experiences2013In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, no Suppl. 2, p. S510-S510Article in journal (Other academic)
  • 14.
    Andersson, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Johansson, Silvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikehult, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Patient expectations and experiences of 18F-FDG-PET-CT: A need for improvement2012In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 39, no S2, p. S207-S207Article in journal (Other academic)
  • 15.
    Andersson, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, Mölndal, Sweden.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, Mölndal, Sweden.
    Separation of water and fat signal in whole-body gradient echo scans using convolutional neural networks2019In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 82, no 3, p. 1177-1186Article in journal (Refereed)
    Abstract [en]

    Purpose: To perform and evaluate water–fat signal separation of whole‐body gradient echo scans using convolutional neural networks.

    Methods: Whole‐body gradient echo scans of 240 subjects, each consisting of 5 bipolar echoes, were used. Reference fat fraction maps were created using a conventional method. Convolutional neural networks, more specifically 2D U‐nets, were trained using 5‐fold cross‐validation with 1 or several echoes as input, using the squared difference between the output and the reference fat fraction maps as the loss function. The outputs of the networks were assessed by the loss function, measured liver fat fractions, and visually. Training was performed using a graphics processing unit (GPU). Inference was performed using the GPU as well as a central processing unit (CPU).

    Results: The loss curves indicated convergence, and the final loss of the validation data decreased when using more echoes as input. The liver fat fractions could be estimated using only 1 echo, but results were improved by use of more echoes. Visual assessment found the quality of the outputs of the networks to be similar to the reference even when using only 1 echo, with slight improvements when using more echoes. Training a network took at most 28.6 h. Inference time of a whole‐body scan took at most 3.7 s using the GPU and 5.8 min using the CPU.

    Conclusion: It is possible to perform water–fat signal separation of whole‐body gradient echo scans using convolutional neural networks. Separation was possible using only 1 echo, although using more echoes improved the results.

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  • 16.
    Andersson, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, Molndal, Sweden.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, Molndal, Sweden.
    Water-fat separation incorporating spatial smoothing is robust to noise2018In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 50, p. 78-83, article id S0730-725X(18)30040-7Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To develop and evaluate a noise-robust method for reconstruction of water and fat images for spoiled gradient multi-echo sequences.

    METHODS: The proposed method performs water-fat separation by using a graph cut to minimize an energy function consisting of unary and binary terms. Spatial smoothing is incorporated to increase robustness to noise. The graph cut can fail to find a solution covering the entire image, in which case the relative weighting of the unary term is iteratively increased until a complete solution is found. The proposed method was compared to two previously published methods. Reconstructions were performed on 16 cases taken from the 2012 ISMRM water-fat reconstruction challenge dataset, for which reference reconstructions were provided. Robustness towards noise was evaluated by reconstructing images with different levels of noise added. The percentage of water-fat swaps were calculated to measure performance.

    RESULTS: At low noise levels the proposed method produced similar results to one of the previously published methods, while outperforming the other. The proposed method significantly outperformed both of the previously published methods at moderate and high noise levels.

    CONCLUSION: By incorporating spatial smoothing, an increased robustness towards noise is achieved when performing water-fat reconstruction of spoiled gradient multi-echo sequences.

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  • 17.
    Andersson, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lundström, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engström, Mathias
    GE Healthcare.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical.
    Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 12358Article in journal (Refereed)
    Abstract [en]

    Brown adipose tissue (BAT) expends chemical energy to produce heat, which makes it a potential therapeutic target for combating metabolic dysfunction and overweight/obesity by increasing its metabolic activity. The most well-established method for measuring BAT metabolic activity is glucose uptake rate (GUR) measured using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). However, this is expensive and exposes the subjects to potentially harmful radiation. Cheaper and safer methods are warranted for large-scale or longitudinal studies. Potential alternatives include infrared thermography (IRT) and magnetic resonance imaging (MRI). The aim of this study was to evaluate and further develop these techniques. Twelve healthy adult subjects were studied. The BAT GUR was measured using 18F-FDG PET during individualized cooling. The temperatures of the supraclavicular fossae and a control region were measured using IRT during a simple cooling protocol. The fat fraction and effective transverse relaxation rate of BAT were measured using MRI without any cooling intervention. Simple and multiple linear regressions were employed to evaluate how well the MRI and IRT measurements could estimate the GUR. Results showed that both IRT and MRI measurements correlated with the GUR. This suggest that these measurements may be suitable for estimating the cold-induced BAT GUR in future studies.

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  • 18.
    Andersson, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Roswall, Josefine
    Hallands Hosp Halmstad, Dept Pediat, Halmstad, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden.
    Kjellberg, Emma
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, Molndal, Sweden.
    Dahlgren, Jovanna
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, Molndal, Sweden.
    MRI estimates of brown adipose tissue in children - Associations to adiposity, osteocalcin, and thigh muscle volume2019In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 58, p. 135-142Article in journal (Refereed)
    Abstract [en]

    Context: Brown adipose tissue is of metabolic interest. The tissue is however poorly explored in children.

    Methods: Sixty-three 7-year old subjects from the Swedish birth-cohort Halland Health and Growth Study were recruited. Care was taken to include both normal weight and overweight children, but the subjects were otherwise healthy. Only children born full term were included. Water-fat separated whole-body MRI scans, anthropometric measurements, and measurements of fasting glucose and levels of energy homeostasis related hormones, including the insulin-sensitizer osteocalcin, were performed. The fat fraction (FF) and effective transverse relaxation time (T-2(star)) of suspected brown adipose tissue in the cervical-supraclavicular-axillary fat depot (sBAT) and the FFs of abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) were measured. Volumes of sBAT, abdominal VAT and SAT, and thigh muscle volumes were measured.

    Results: The FF in the sBAT depot was lower than in VAT and SAT for all children. In linear correlations including sex and age as explanatory variables, sBAT FF correlated positively with all measures of adiposity (p < 0.01), except for VAT FF and weight, positively with sBAT T-2* (p = 0.036), and negatively with osteocalcin (p = 0.017). When adding measures of adiposity as explanatory variables, sBAT FF also correlated negatively with thigh muscle volume (p < 0.01).

    Conclusions: Whole-body water-fat MRI of children allows for measurements of sBAT. The FF of sBAT was lower than that of VAT and SAT, indicating presence of BAT. Future studies could confirm whether the observed correlations corresponds to a hormonally active BAT.

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  • 19.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Burgos, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kempton, Matthew J
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Craft, Suzanne
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Impaired Insulin Sensitivity as Indexed by the HOMA Score Is Associated With Deficits in Verbal Fluency and Temporal Lobe Gray Matter Volume in the Elderly2012In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 35, no 3, p. 488-494Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    Impaired insulin sensitivity is linked to cognitive deficits and reduced brain size. However, it is not yet known whether insulin sensitivity involves regional changes in gray matter volume. Against this background, we examined the association between insulin sensitivity, cognitive performance, and regional gray matter volume in 285 cognitively healthy elderly men and women aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.

    RESEARCH DESIGN AND METHODS

    Insulin sensitivity was calculated from fasting serum insulin and plasma glucose determinations using the homeostasis model assessment of insulin resistance (HOMA-IR) method. Cognitive performance was examined by a categorical verbal fluency. Participants also underwent a magnetic resonance imaging (MRI) brain scan. Multivariate analysis using linear regression was conducted, controlling for potential confounders (sex, education, serum LDL cholesterol, mean arterial blood pressure, and abdominal visceral fat volume).

    RESULTS

    The HOMA-IR was negatively correlated with verbal fluency performance, brain size (S1), and temporal lobe gray matter volume in regions known to be involved in speech production (Brodmann areas 21 and 22, respectively). No such effects were observed when examining diabetic (n = 55) and cognitively impaired (n = 27) elderly subjects as separate analyses.

    CONCLUSIONS

    These cross-sectional findings suggest that both pharmacologic and lifestyle interventions improving insulin signaling may promote brain health in late life but must be confirmed in patient studies.

  • 20.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Burgos, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Le Grevès, Madeleine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Association between physical activity and brain health in older adults2013In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 34, no 1, p. 83-90Article in journal (Refereed)
    Abstract [en]

    In the present cross-sectional study, we examined physical activity (PA) and its possible association with cognitive skills and brain structure in 331 cognitively healthy elderly. Based on the number of self-reported light and hard activities for at least 30 minutes per week, participants were assigned to 4 groups representing different levels of PA. The cognitive skills were assessed by the Mini Mental State Examination score, a verbal fluency task, and the Trail-making test as a measure of visuospatial orientation ability. Participants also underwent a magnetic resonance imaging of the brain. Multiple regression analysis revealed that greater PA was associated with a shorter time to complete the Trail-making test, and higher levels of verbal fluency. Further, the level of self-reported PA was positively correlated with brain volume, white matter, as well as a parietal lobe gray matter volume, situated bilaterally at the precuneus. These present cross-sectional results indicate that PA is a lifestyle factor that is linked to brain structure and function in late life.

  • 21.
    Berglund, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Two-point dixon method with flexible echo times2011In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 65, no 4, p. 994-1004Article in journal (Refereed)
    Abstract [en]

    The two-point Dixon method is a proton chemical shift imaging technique that produces separated water-only and fat-only images from a dual-echo acquisition. It is shown how this can be achieved without the usual constraints on the echo times. A signal model considering spectral broadening of the fat peak is proposed for improved water/fat separation. Phase errors, mostly due to static field inhomogeneity, must be removed prior to least-squares estimation of water and fat. To resolve ambiguity of the phase errors, a corresponding global optimization problem is formulated and solved using a message-passing algorithm. It is shown that the noise in the water and fat estimates matches the Cramér-Rao bounds, and feasibility is demonstrated for in vivo abdominal breath-hold imaging. The water-only images were found to offer superior fat suppression compared with conventional spectrally fat suppressed images.

  • 22.
    Berglund, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Model-based mapping of fat unsaturation and chain length by chemical shift imaging: phantom validation and in vivo feasibility2012In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 68, no 6, p. 1815-1827Article in journal (Refereed)
    Abstract [en]

    Knowledge about the triglyceride (fat) 1H spectrum enables quantitative determination of several triglyceride characteristics. This work describes a model-based chemical shift imaging method that separates water and fat signal and provides maps of three triglyceride quantities: fatty acid carbon chain length (CL), number of double bond pairs (ndb), and number of methylene-interrupted double bonds (nmidb). The method was validated by imaging a phantom containing ten different oils using 1.5 T and 3.0 T clinical scanners, with gas-liquid chromatography (GLC) as reference. Repeated acquisitions demonstrated high reproducibility of the method. Statistical tests of correlation and linear regression were performed to examine the accuracy of the method. Significant correlation was found at both field strengths for all three quantities, and high correlation (r2 > 0.96) was found for measuring ndb and nmidb. Feasibility of the method for in vivo imaging of the thigh was demonstrated at both field strengths. The estimates of ndb and nmidb in subcutaneous adipose tisse were in agreement with literature values, while CL appears overestimated. The method has potential use in large-scale cross-sectional and longitudinal studies of triglyceride composition, and its relation to diet and various diseases.

  • 23.
    Berglund, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Three-point Dixon method enables whole-body water and fat imaging of obese subjects2010In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 63, no 6, p. 1659-1668Article in journal (Refereed)
    Abstract [en]

    Dixon imaging techniques derive chemical shift-separated water and fat images, enabling the quantification of fat content and forming an alternative to fat suppression. Whole-body Dixon imaging is of interest in studies of obesity and the metabolic syndrome, and possibly in oncology. A three-point Dixon method is proposed where two solutions are found analytically in each voxel. The true solution is identified by a multiseed three-dimensional region-growing scheme with a dynamic path, allowing confident regions to be solved before unconfident regions, such as background noise. 2 pi-Phase unwrapping is not required. Whole-body datasets (256 x 184 x 252 voxels) were collected from 39 subjects (body mass index 19.8-45.4 kg/m(2)), in a mean scan time of 5 min 15 sec. Water and fat images were reconstructed offline, using the proposed method and two reference methods. The resulting images were subjectively graded on a four-grade scale by two radiologists, blinded to the method used. The proposed method was found superior to the reference methods. It exclusively received the two highest grades, implying that only mild reconstruction failures were found. The computation time for a whole-body dataset was 1 min 51.5 sec +/- 3.0 sec. It was concluded that whole-body water and fat imaging is feasible even for obese subjects, using the proposed method.

  • 24.
    Bergstrom, Goran
    et al.
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Clin Physiol, Gothenburg, Sweden..
    Persson, Margaretha
    Lund Univ, Dept Clin Sci, Malmö, Sweden.;Skane Univ Hosp, Dept Internal Med, Malmö, Sweden..
    Adiels, Martin
    Univ Gothenburg, Inst Med, Sch Publ Hlth & Community Med, Gothenburg, Sweden..
    Bjornson, Elias
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden..
    Bonander, Carl
    Univ Gothenburg, Inst Med, Sch Publ Hlth & Community Med, Gothenburg, Sweden..
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Alfredsson, Joakim
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden..
    Angeras, Oskar
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Cardiol, Gothenburg, Sweden..
    Berglund, Goran
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Blomberg, Anders
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Brandberg, John
    Sahlgrens Acad, Dept Radiol, Inst Clin Sci, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Radiol, Gothenburg, Sweden..
    Borjesson, Mats
    Sahlgrens Acad, Inst Med, Gothenburg, Sweden.;Univ Gothenburg, Ctr Hlth & Performance, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Cederlund, Kerstin
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden..
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Olov.Duvernoy@radiol.uu.se.
    Ekblom, Orjan
    Swedish Sch Sport & Hlth Sci GIH, Dept Phys Act & Hlth, Stockholm, Sweden..
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Engvall, Jan E.
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Clin Physiol, Linköping, Sweden.;Linköping Univ, CMIV, Ctr Med Image Sci & Visualizat, Linköping, Sweden..
    Fagman, Erika
    Sahlgrens Acad, Dept Radiol, Inst Clin Sci, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Radiol, Gothenburg, Sweden..
    Eriksson, Mats
    Karolinska Univ Hosp Huddinge, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.;Karolinska Univ Hosp Huddinge, Clin Res Ctr, Stockholm, Sweden..
    Erlinge, David
    Lund Univ, Cardiol, Dept Clin Sci Lund, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Fagerberg, Bjorn
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Flinck, Agneta
    Sahlgrens Acad, Dept Radiol, Inst Clin Sci, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Radiol, Gothenburg, Sweden..
    Goncalves, Isabel
    Lund Univ, Dept Clin Sci Malmö, Lund, Sweden..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hjelmgren, Ola
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Clin Physiol, Gothenburg, Sweden..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lindqvist, Per
    Umeå Univ, Dept Surg & Perioperat Sci, Umeå, Sweden..
    Ljungberg, Johan
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Magnusson, Martin
    Lund Univ, Dept Clin Sci, Malmö, Sweden.;Skane Univ Hosp, Dept Cardiol, Malmö, Sweden.;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden.;North West Univ, Hypertens Africa Res Team HART, Potchefstroom, South Africa..
    Mannila, Maria
    Karolinska Univ Hosp, Dept Cardiol & Clin Genet, Heart & Vasc Theme, Stockholm, Sweden..
    Markstad, Hanna
    Lund Univ, Clin Sci Malmö, Clin Res Ctr, Expt Cardiovasc Res, Malmö, Sweden.;Lund Univ, Ctr Med Imaging & Physiol, Lund, Sweden..
    Mohammad, Moman A.
    Lund Univ, Cardiol, Dept Clin Sci Lund, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Nystrom, Fredrik H.
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden..
    Ostenfeld, Ellen
    Skane Univ Hosp, Lund, Sweden.;Lund Univ, Dept Clin Sci Lund, Clin Physiol, Lund, Sweden..
    Persson, Anders
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Radiol, Linköping, Sweden.;Linköping Univ, CMIV, Ctr Med Image Sci & Visualizat, Linköping, Sweden..
    Rosengren, Annika
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Sandstrom, Anette
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Sjalander, Anders
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Skold, Magnus C.
    Karolinska Inst, Dept Med Solna, Resp Med Unit, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Resp Med & Allergy, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia..
    Swahn, Eva
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden..
    Soderberg, Stefan
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Toren, Kjell
    Univ Gothenburg, Sch Publ Hlth & Community Med, Occupat & Environm Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Ostgren, Carl Johan
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, CMIV, Ctr Med Image Sci & Visualizat, Linköping, Sweden..
    Jernberg, Tomas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population2021In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 144, no 12, p. 916-929Article in journal (Refereed)
    Abstract [en]

    Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population. Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or >= 50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data. Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (>= 50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population. Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.

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  • 25. Bergström, Mats
    et al.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lindner, K J
    Bjurling, Pernilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    In vivo demonstration of enzyme activity in endocrine pancreatic tumors: decarboxylation of carbon-11-DOPA to carbon-11-dopamine1996In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 37, no 1, p. 32-37Article in journal (Refereed)
    Abstract [en]

    METHODS:

    We used PET to characterize the uptake and decarboxylation of 11C-L-DOPA in vivo in two patients with endocrine pancreatic tumors: one glucagonoma and one gastrinoma.

    RESULTS:

    With L-DOPA labeled with 11C in the beta position, in which the radioactive label follows the molecule through decarboxylation to dopamine, significant uptake was observed in the tumors. With L-DOPA labeled in the carboxyl group, in which the label is rapidly eliminated from the tissue as 11CO2 if decarboxylation takes place, an almost complete lack of uptake is noted.

    CONCLUSION:

    This study shows that, using selective position labeling, an in vivo action of enzymatic activity can be observed with PET and that significant decarboxylation occurs in the tested endocrine pancreatic tumors. Also, marked retention of radioactivity occurs after treatment with somatostatin analogs. It is hypothesized that this is a reflection of a reduction of exocytosis which is induced by this treatment.

  • 26.
    Bjermo, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Center for Clinical Research Dalarna.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Dahlman, Ingrid
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Persson, Lena
    Berglund, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Pulkki, Kari
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Uusitupa, Matti
    Rudling, Mats
    Arner, Peter
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial2012In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 95, no 5, p. 1003-1012Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Replacing SFAs with vegetable PUFAs has cardiometabolic benefits, but the effects on liver fat are unknown. Increased dietary n-6 PUFAs have, however, also been proposed to promote inflammation-a yet unproven theory.

    OBJECTIVE:

    We investigated the effects of PUFAs on liver fat, systemic inflammation, and metabolic disorders.

    DESIGN:

    We randomly assigned 67 abdominally obese subjects (15% had type 2 diabetes) to a 10-wk isocaloric diet high in vegetable n-6 PUFA (PUFA diet) or SFA mainly from butter (SFA diet), without altering the macronutrient intake. Liver fat was assessed by MRI and magnetic resonance proton (1H) spectroscopy (MRS). Proprotein convertase subtilisin/kexin type-9 (PCSK9, a hepatic LDL-receptor regulator), inflammation, and adipose tissue expression of inflammatory and lipogenic genes were determined.

    RESULTS:

    A total of 61 subjects completed the study. Body weight modestly increased but was not different between groups. Liver fat was lower during the PUFA diet than during the SFA diet [between-group difference in relative change from baseline; 16% (MRI; P < 0.001), 34% (MRS; P = 0.02)]. PCSK9 (P = 0.001), TNF receptor-2 (P < 0.01), and IL-1 receptor antagonist (P = 0.02) concentrations were lower during the PUFA diet, whereas insulin (P = 0.06) tended to be higher during the SFA diet. In compliant subjects (defined as change in serum linoleic acid), insulin, total/HDL-cholesterol ratio, LDL cholesterol, and triglycerides were lower during the PUFA diet than during the SFA diet (P < 0.05). Adipose tissue gene expression was unchanged.

    CONCLUSIONS:

    Compared with SFA intake, n-6 PUFAs reduce liver fat and modestly improve metabolic status, without weight loss. A high n-6 PUFA intake does not cause any signs of inflammation or oxidative stress. Downregulation of PCSK9 could be a novel mechanism behind the cholesterol-lowering effects of PUFAs.

  • 27.
    Bjerner, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ericsson, Anders
    Briley-Soebo, Karen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bjørnerud, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    In and ex vivo MR evaluation of acute myocardial ischemia in pigs by determining R1 in steady state after the administration of the intravascular contrast agent NC100150 injection2004In: Investigative Radiology, ISSN 0020-9996, E-ISSN 1536-0210, Vol. 39, no 8, p. 479-486Article in journal (Refereed)
  • 28.
    Bjerner, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    High in-plane resolution T2-weighted magnetic resonance imaging of acute myocardial ischemia in pigs using the intravascular contrast agent NC100150 injection.2004In: Investigative Radiology, ISSN 0020-9996, E-ISSN 1536-0210, Vol. 39, no 8, p. 470-478Article in journal (Refereed)
    Abstract [en]

    Rationale and Objectives: The intravascular contrast agent NC100150 injection was tested for its ability to demarcate nonperfused myocardium in a porcine model of coronary occlusion.

    Materials and Methods: A T2-weighted fast spin echo sequence was acquired ex vivo and in vivo during first pass and steady-state circulation of the contrast agent in 2 dosages (2 and 5 mg Fe/kg bw) or saline.

    Results: Ex vivo, in the high-dose group, the volume of nonperfused myocardium determined from T2-weighted images was 99% of that determined from photographs where perfused myocardium stained with fluorescein. A significantly higher contrast to noise ratio between perfused and nonperfused myocardium was found (both ex and in vivo in steady state) compared with the control group. During first pass, a significant reduction in signal intensity (74 ± 18%) was found in perfused myocardium after contrast injection.

    Conclusion: NC100150 injection, combined with T2-weighted turbo spin echo imaging, allowed detailed visualization of non-perfused myocardium in the steady state, which corresponded to the area at risk as determined by fluorescein.

  • 29.
    Björnerud, Atle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Assessment of myocardial blood volume and water exchange: theoretical considerations and in vivo results.2003In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 49, no 5, p. 828-837Article in journal (Refereed)
  • 30.
    Bjørnerud, A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Radiologi.
    Johansson, Lars O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlstrom, Håkan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Pre-clinical results with Clariscan (NC100150 Injection): experience from different disease models2001In: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 12, no 2-3, p. 99-103Article in journal (Other academic)
    Abstract [en]

    A superparamagnetic nanoparticle (NC100150 Injection) was investigated in two different animal models; renal perfusion in pigs and tumour imaging in mice. In the pig model, qualitative first-pass perfusion maps following a bolus injection of NC100150 Injection enabled good visualisation of hypoperfused regions of the renal cortex following partial ligation of the renal artery. High temporal resolution was found to be essential to accurately capture the first passage of the contrast agent through the kidney due to the very rapid blood flow in normal renal cortex. In the tumour model (LS174T cells implanted in nude mice), NC100150 Injection was found to cause a gradual (over 60 min) signal increase on T1-w images in part of the tumours which was attributed to contrast agent leakage from the vascular space to the extravascular space in areas of increased capillary permeability. This observation is consistent with previous reports on the molecular cut-off size for vascular extraction for this tumour cell line. The specific enhancement of tumour tissue suggest potential utility of NC100150 Injection as an angiogenesis marker.

  • 31.
    Bjørnerud, Atle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Renal T(*)(2) perfusion using an iron oxide nanoparticle contrast agent: influence of T(1) relaxation on the first-pass response2002In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 47, no 2, p. 298-304Article in journal (Refereed)
    Abstract [en]

    Quantitative perfusion measurements require accurate knowledge of the correlation between first-pass signal changes and the corresponding tracer concentration in tissue. In the present study, a detailed analysis of first-pass renal cortical changes in T(1) and T(*)(2) following bolus injection of the iron oxide nanoparticle NC100150 Injection was investigated in a pig model using a double-echo gradient-echo sequence. The estimated change in 1/T(*)(2) during first pass calculated from single-echo sequences was compared to the true double-echo-derived 1/T(*)(2) curves. Using a single-echo (TE = 6 ms) spoiled gradient-echo sequence, the first-pass 1/T(*)(2) response following a bolus injection of 1 mg Fe/kg of NC100150 Injection was significantly underestimated due to counteracting T(1) effects. Signal response simulations showed that the relative error in the first-pass response decreased with increasing TE and contrast agent dose. However, both the maximum TE and the maximum dose are limited by excessive cortical signal loss, and the maximum TE is further limited by high temporal resolution requirements. The problem of T(1) contamination can effectively be overcome by using a double-echo gradient-echo sequence. This yields a first-pass response that truly reflects the tissue tracer concentration, which is a critical requirement for quantitative renal perfusion assessment.

  • 32.
    Bjørnerud, Atle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Radiologi.
    Johansson, Lars O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Briley-Sæbø, Karen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Radiologi.
    Ahlström, Håkan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Assessment of T1 and T2* effects in vivo and ex vivo using iron oxide nanoparticles in steady state: dependence on blood volume and water exchange2002In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 47, no 3, p. 461-471Article in journal (Refereed)
    Abstract [en]

    Accurate knowledge of the relationship between contrast agent concentration and tissue relaxation is a critical requirement for quantitative assessment of tissue perfusion using contrast-enhanced MRI. In the present study, using a pig model, the relationship between steady-state blood concentration levels of an iron oxide nanoparticle with a hydrated diameter of 12 nm (NC100150 Injection) and changes in the transverse and longitudinal relaxation rates (1/T2* and 1/T1, respectively) in blood, muscle, and renal cortex was investigated at 1.5 T. Ex vivo measurements of 1/T2* and 1/T1 were additionally performed in whole pig blood spiked with different concentrations of the iron oxide nanoparticle. In renal cortex and muscle, 1/T2* increased linearly with contrast agent concentration with slopes of 101 +/-22 s(-1)mM(-1) and 6.5 +/-0.9 s(-1)mM(-1) (mean +/- SD), respectively. In blood, 1/T2* increased as a quadratic function of contrast agent concentration, with different quadratic terms in the ex vivo vs. the in vivo experiments. In vivo, 1/T1 in blood increased linearly with contrast agent concentration, with a slope (T1-relaxivity) of 13.9 +/- 0.9 s(-1)mM(-1). The achievable increase in 1/T1 in renal cortex and muscle was limited by the rate of water exchange between the intra- and extravascular compartments and the 1/T1-curves were well described by a two-compartment water exchange limited relaxation model.

  • 33.
    Boersma, Greta J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Heurling, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Johansson, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lau Börjesson, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skrtic, S.
    AstraZeneca, R&D, Gothenburg, Sweden.;AstraZeneca, Dept Med, Gothenburg, Sweden..
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Glucose uptake in skeletal muscle, brain and visceral adipose tissue assessed with PET/MR strongly predicts whole body glucose uptake during hyperinsulinaemia2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S80-S80Article in journal (Other academic)
  • 34.
    Boersma, Greta J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Johansson, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Heurling, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Wallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry, University of Gothenburg, Sweden.
    Skrtic, Stanko
    Lau, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Panagiotou, Grigorios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, Mölndal, Sweden.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, Mölndal, Sweden.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study2018In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 50, no 8, p. 627-639Article in journal (Refereed)
    Abstract [en]

    We assessed glucose uptake in different tissues in type 2 diabetes (T2D), prediabetes, and control subjects to elucidate its impact in the development of whole-body insulin resistance and T2D. Thirteen T2D, 12 prediabetes, and 10 control subjects, matched for age and BMI, underwent OGTT and abdominal subcutaneous adipose tissue (SAT) biopsies. Integrated whole-body 18F-FDG PET and MRI were performed during a hyperinsulinemic euglycemic clamp to asses glucose uptake rate (MRglu) in several tissues. MRglu in skeletal muscle, SAT, visceral adipose tissue (VAT), and liver was significantly reduced in T2D subjects and correlated positively with M-values (r=0.884, r=0.574, r=0.707 and r=0.403, respectively). Brain MRglu was significantly higher in T2D and prediabetes subjects and had a significant inverse correlation with M-values (r=-0.616). Myocardial MRglu did not differ between groups and did not correlate with the M-values. A multivariate model including skeletal muscle, brain and VAT MRglu best predicted the M-values (adjusted r2=0.85). In addition, SAT MRglu correlated with SAT glucose uptake ex vivo (r=0.491). In different stages of the development of T2D, glucose uptake during hyperinsulinemia is elevated in the brain in parallel with an impairment in peripheral organs. Impaired glucose uptake in skeletal muscle and VAT together with elevated glucose uptake in brain were independently associated with whole-body insulin resistance, and these tissue-specific alterations may contribute to T2D development.

  • 35.
    Boersma, Greta J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Johansson, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skrtic, S.
    AstraZeneca, R&D, Gothenburg, Sweden.;Univ Gothenburg, Dept Med, Gothenburg, Sweden..
    Lau Börjesson, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Panagiotou, G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skeletal muscle and liver, but not brain, account for impaired glucose utilisation in type 2 diabetes: whole-body PET/MR during hyperinsulinaemic euglycaemic clamp2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, p. S33-S33Article in journal (Refereed)
  • 36.
    Boone, Sebastiaan C.
    et al.
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Postal Zone C7-P,POB 9600, NL-2300 RC Leiden, Netherlands..
    van Smeden, Maarten
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Postal Zone C7-P,POB 9600, NL-2300 RC Leiden, Netherlands.;Leiden Univ, Dept Biomed Data Sci, Med Stat & Bioinformat Sect, Med Ctr, Leiden, Netherlands..
    Rosendaal, Frits R.
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Postal Zone C7-P,POB 9600, NL-2300 RC Leiden, Netherlands..
    le Cessie, Saskia
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Postal Zone C7-P,POB 9600, NL-2300 RC Leiden, Netherlands.;Leiden Univ, Dept Biomed Data Sci, Med Stat & Bioinformat Sect, Med Ctr, Leiden, Netherlands..
    Groenwold, Rolf H. H.
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Postal Zone C7-P,POB 9600, NL-2300 RC Leiden, Netherlands..
    Jukema, J. Wouter
    Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.;Netherlands Heart Inst, Utrecht, Netherlands..
    van Dijk, Ko Willems
    Leiden Univ, Dept Human Genet, Med Ctr, Leiden, Netherlands.;Leiden Univ, Einthoven Lab Expt Vasc Med, Med Ctr, Leiden, Netherlands.;Leiden Univ, Dept Med, Div Endocrinol, Med Ctr, Leiden, Netherlands..
    Lamb, Hildo J.
    Leiden Univ, Dept Radiol, Med Ctr, Leiden, Netherlands..
    Greenland, Philip
    Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA..
    Neeland, Ian J.
    Univ Hosp Harrington Heart & Vasc Inst, Div Cardiovasc Dis, Cleveland, OH USA.;Case Western Reserve Univ, Sch Med, Div Cardiovasc Dis, Cleveland, OH USA..
    Allison, Matthew A.
    Univ Calif San Diego, Dept Family Med & Publ Hlth, Div Prevent Med, San Diego, CA 92103 USA..
    Criqui, Michael H.
    Univ Calif San Diego, Dept Family Med & Publ Hlth, Div Prevent Med, San Diego, CA 92103 USA..
    Budoff, Matthew J.
    Harbor UCLA Med Ctr, Dept Med, Lundquist Inst, Torrance, CA 90509 USA..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med AB, Mölndal, Sweden..
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med AB, Mölndal, Sweden..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Postal Zone C7-P,POB 9600, NL-2300 RC Leiden, Netherlands.;Leiden Univ, Dept Publ Hlth & Primary Care, Med Ctr, Leiden, Netherlands..
    de Mutsert, Renee
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Postal Zone C7-P,POB 9600, NL-2300 RC Leiden, Netherlands..
    Evaluation of the Value of Waist Circumference and Metabolomics in the Estimation of Visceral Adipose Tissue2022In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 191, no 5, p. 886-899Article in journal (Refereed)
    Abstract [en]

    Visceral adipose tissue (VAT) is a strong prognostic factor for cardiovascular disease and a potential target for cardiovascular risk stratification. Because VAT is difficult to measure in clinical practice, we estimated prediction models with predictors routinely measured in general practice and VAT as outcome using ridge regression in 2,501 middle-aged participants from the Netherlands Epidemiology of Obesity study, 2008-2012. Adding waist circumference and other anthropometric measurements on top of the routinely measured variables improved the optimism-adjusted R-2 from 0.50 to 0.58 with a decrease in the root-mean-square error (RMSE) from 45.6 to 41.5 cm(2) and with overall good calibration. Further addition of predominantly lipoprotein-related metabolites from the Nightingale platform did not improve the optimism-corrected R-2 and RMSE. The models were externally validated in 370 participants from the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS, 2006-2009) and 1,901 participants from the Multi-Ethnic Study of Atherosclerosis (MESA, 2000-2007). Performance was comparable to the development setting in PIVUS (R-2 = 0.63, RMSE = 42.4 cm(2), calibration slope = 0.94) but lower in MESA (R-2 = 0.44, RMSE = 60.7 cm(2), calibration slope = 0.75). Our findings indicate that the estimation of VAT with routine clinical measurements can be substantially improved by incorporating waist circumference but not by metabolite measurements.

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  • 37.
    Breznik, Eva
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Multiple comparison correction methods for whole-body magnetic resonance imaging2020In: Journal of Medical Imaging, ISSN 2329-4302, E-ISSN 2329-4310, Vol. 7, no 1, article id 014005Article in journal (Refereed)
    Abstract [en]

    Purpose: Voxel-level hypothesis testing on images suffers from test multiplicity. Numerous correction methods exist, mainly applied and evaluated on neuroimaging and synthetic datasets. However, newly developed approaches like Imiomics, using different data and less common analysis types, also require multiplicity correction for more reliable inference. To handle the multiple comparisons in Imiomics, we aim to evaluate correction methods on whole-body MRI and correlation analyses, and to develop techniques specifically suited for the given analyses. Approach: We evaluate the most common familywise error rate (FWER) limiting procedures on whole-body correlation analyses via standard (synthetic no-activation) nominal error rate estimation as well as smaller prior-knowledge based stringency analysis. Their performance is compared to our anatomy-based method extensions. Results: Results show that nonparametric methods behave better for the given analyses. The proposed prior-knowledge based evaluation shows that the devised extensions including anatomical priors can achieve the same power while keeping the FWER closer to the desired rate. Conclusions: Permutation-based approaches perform adequately and can be used within Imiomics. They can be improved by including information on image structure. We expect such method extensions to become even more relevant with new applications and larger datasets.

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  • 38.
    Briley Saebo, Karen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bjørnerud, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Grant, Derek
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Berg, Trond
    Mörk Kindberg, Grete
    Hepatic cellular distribution and degradation of iron oxide nanoparticles following single intravenous injection in rats: implications for magnetic resonance imaging2004In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 316, no 3, p. 315-323Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to determine the cellular distribution and degradation in rat liver following intravenous injection of superparamagnetic iron oxide nanoparticles used for magnetic resonance imaging (NC100150 Injection). Relaxometric and spectrophotometric methods were used to determine the concentration of the iron oxide nanoparticles and their degradation products in isolated rat liver parenchymal, endothelial and Kupffer cell fractions. An isolated cell phantom was also constructed to quantify the effect of the degradation products on the loss of MR signal in terms of decreased transverse relaxation times, T2*. The results of this study show that iron oxide nanoparticles found in the NC100150 Injection were taken up and distributed equally in both liver endothelial and Kupffer cells following a single 5 mg Fe/kg body wt. bolus injection in rats. Whereas endothelial and Kupffer cells exhibited similar rates of uptake and degradation, liver parenchymal cells did not take up the NC100150 Injection iron oxide particles. Light-microscopy methods did, however, indicate an increased iron load, presumably as ferritin/hemosiderin, within the hepatocytes 24 h post injection. The study also confirmed that compartmentalisation of ferritin/hemosiderin may cause a significant decrease in the MRI signal intensity of the liver. In conclusion, the combined results of this study imply that the prolonged presence of breakdown product in the liver may cause a prolonged imaging effect (in terms of signal loss) for a time period that significantly exceeds the half-life of NC100150 Injection iron oxide nanoparticles in liver.

  • 39.
    Brooks, Samantha J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Burgos, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kempton, M J
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Late-life obesity is associated with smaller global and regional gray matter volumes: a voxel-based morphometric study2013In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 37, no 2, p. 230-236Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: 

    Obesity adversely affects frontal lobe brain structure and function. Here we sought to show that people who are obese versus those who are of normal weight over a 5-year period have differential global and regional brain volumes.

    DESIGN: 

    Using voxel-based morphometry, contrasts were done between those who were recorded as being either obese or of normal weight over two time points in the 5 years prior to the brain scan. In a post-hoc preliminary analysis, we compared scores for obese and normal weight people who completed the trail-making task.

    SUBJECTS: 

    A total of 292 subjects were examined following exclusions (for example, owing to dementia, stroke and cortical infarcts) from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort with a body mass index of normal weight (<25 kg m−2) or obese (30 kg m−2).

    RESULTS: 

    People who were obese had significantly smaller total brain volumes and specifically, significantly reduced total gray matter (GM) volume (GMV) (with no difference in white matter or cerebrospinal fluid). Initial exploratory whole brain uncorrected analysis revealed that people who were obese had significantly smaller GMV in the bilateral supplementary motor area, bilateral dorsolateral prefrontal cortex (DLPFC), left inferior frontal gyrus and left postcentral gyrus. Secondary more stringent corrected analyses revealed a surviving cluster of GMV difference in the left DLPFC. Finally, post-hoc contrasts of scores on the trail-making task, which is linked to DLPFC function, revealed that obese people were significantly slower than those of normal weight.

    CONCLUSION: 

    These findings suggest that in comparison with normal weight, people who are obese have smaller GMV, particularly in the left DLPFC. Our results may provide evidence for a potential working memory mechanism for the cognitive suppression of appetite that may lower the risk of developing obesity in later life.

  • 40.
    Carlbom, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Caballero-Corbalán, José
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Whole-body MRI including diffusion-weighted MRI compared with 5-HTP PET/CT in the detection of neuroendocrine tumors2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 1, p. 43-50Article in journal (Refereed)
    Abstract [en]

    AIM: We wanted to explore if whole-body magnetic resonance imaging (MRI) including diffusion-weighted (DW) and liver-specific contrast agent-enhanced imaging could be valuable in lesion detection of neuroendocrine tumors (NET). [11C]-5-Hydroxytryptophan positron emission tomography/computed tomography (5-HTP PET/CT) was used for comparison.

    MATERIALS AND METHODS: Twenty-one patients with NET were investigated with whole-body MRI, including DW imaging (DWI) and contrast-enhanced imaging of the liver, and whole-body 5-HTP PET/CT. Seven additional patients underwent upper abdomen MRI including DWI, liver-specific contrast agent-enhanced imaging, and 5-HTP PET/CT.

    RESULTS: There was a patient-based concordance of 61% and a lesion-based concordance of 53% between the modalities. MRI showed good concordance with PET in detecting bone metastases but was less sensitive in detecting metastases in mediastinal lymph nodes. MRI detected more liver metastases than 5-HTP PET/CT.

    CONCLUSION: Whole-body MRI with DWI did not detect all NET lesions found with whole-body 5-HTP PET/CT. Our findings indicate that MRI of the liver including liver-specific contrast agent-enhanced imaging and DWI could be a useful complement to whole-body 5-HTP PET/CT.

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  • 41.
    Carlbom, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Pancreatic perfusion and subsequent response to glucose in healthy individuals and patients with type 1 diabetes2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, no 9, p. 1968-1972Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: The aim of this study was to investigate pancreatic perfusion and its response to a glucose load in patients with type 1 diabetes mellitus compared with non-diabetic ('healthy') individuals.

    METHODS: Eight individuals with longstanding type 1 diabetes and ten sex-, age- and BMI-matched healthy controls underwent dynamic positron emission tomography scanning with (15)O-labelled water before and after intravenous administration of glucose. Perfusion in the pancreas was measured. Portal and arterial hepatic perfusion were recorded as references.

    RESULTS: Under fasting conditions, total pancreatic perfusion was on average 23% lower in the individuals with diabetes compared with healthy individuals. Glucose increased total pancreatic and portal hepatic blood perfusion in healthy individuals by 48% and 38%, respectively. In individuals with diabetes there was no significant increase in either total pancreatic or portal hepatic perfusion.

    CONCLUSIONS/INTERPRETATION: Individuals with type 1 diabetes have reduced basal pancreatic perfusion and a severely impaired pancreatic and splanchnic perfusion response to intravenous glucose stimulation.

  • 42.
    Carlbom, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    [(11)C]5-Hydroxy-Tryptophan PET for Assessment of Islet Mass During Progression of Type 2 Diabetes2017In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 66, no 5, p. 1286-1292Article in journal (Refereed)
    Abstract [en]

    [(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP) PET of the pancreas has been shown to be a surrogate imaging biomarker of pancreatic islet mass. The change in islet mass in different stages of type 2 diabetes (T2D) as measured by non-invasive imaging is currently unknown. Here, we describe a cross-sectional study where subjects at different stages of T2D development with expected stratification of pancreatic islet mass were examined in relation to non-diabetic individuals. The primary outcome was the [(11)C]5-HTP uptake and retention in pancreas, as a surrogate marker for the endogenous islet mass.We found that metabolic testing indicated a progressive loss of beta cell function, but that this was not mirrored by a decrease in [(11)C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased beta cell function. The results herein indicates that beta cell dedifferentiation, and not necessarily endocrine cell loss, constitute a major cause of beta cell failure in T2D.

  • 43.
    Carlbom, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pre-transplantation ³¹P-magnetic resonance spectroscopy for quality assessment of human pancreatic grafts: A feasibility study2017In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 39, p. 98-102Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the feasibility of using (31)P-MRS for objective non-invasive quality assessment of human pancreas grafts prior to transplantation or islet isolation.

    Materials and methods: Pancreata from 5 human donors, 3 males and 2 females, aged 49-78years, with body mass index (BMI) 22-31kg/m(2), were included. Pancreata were perfused with histidine-tryptophan-ketoglutarate solution during procurement and stored in hypothermic condition (4°C) for 21-44h. During the period of hypothermic storage repeated spectra were obtained for each graft by (31)P-MRS (1.5Tesla) to measure the cold ischemia time (CIT) dependent changes of the phosphorous metabolites adenosine triphosphate (ATP), phosphomonoesters (PME), phosphodiesters (PDE) and inorganic phosphate (Pi), in the grafts. Graft temperature was measured immediately before and after MR-examination. Reference spectrum for non-viable tissue was obtained after graft exposure to room temperature.

    Results: PME/Pi, PDE/Pi and ATP/Pi spectral intensities ratios decreased with increasing CIT, reflecting the decreased viability of the grafts. PME/Pi ratio was the most discriminatory variable at prolonged CIT. (31)P-MRS could be performed without significantly increasing graft temperature.

    Conclusions: (31)P-MRS may provide quantitative parameters for evaluating graft viability ex vivo, and is a promising tool for objective non-invasive assessment of the quality of human pancreas grafts prior to transplantation or islet isolation.

  • 44.
    Carlsson, Per-Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Rotem, Avi
    Zimermann, Baruch
    Grinberg, Helena
    Goldman, Tali
    Barkai, Uriel
    Avni, Yuval
    Westermark, Gunilla T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlbom, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical AB, Mölndal, Sweden.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Olerud, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Transplantation of macroencapsulated human islets within the bioartificial pancreas βAir to patients with type 1 diabetes mellitus2018In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 18, no 7, p. 1735-1744Article in journal (Refereed)
    Abstract [en]

    Macroencapsulation devices provide the dual possibility to immunoprotect transplanted cells while also being retrievable; the latter bearing importance for safety in future trials with stem-cell derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic islets to patients with type 1 diabetes. Four patients were transplanted with 1-2 βAir devices, each containing 155000-180000 IEQ (i.e. 1800-4600 IEQ per kg body weight), and monitored for 3-6 months, followed by the recovery of devices. Implantation of the βAir device was safe and successfully prevented immunization and rejection of the transplanted tissue. However, although beta cells survived in the device, only minute levels of circulating C-peptide were observed with no impact on metabolic control. Fibrotic tissue with immune cells was formed in capsule surroundings. Recovered devices displayed a blunted glucose-stimulated insulin response, and amyloid formation in the endocrine tissue. We conclude that the βAir device is safe and can support survival of allogeneic islets for several months, although the function of the transplanted cells was limited.

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  • 45.
    Christoffersson, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Henriksnäs, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Rolny, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Caballero-Corbalán, José
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Segersvärd, Ralf
    Permert, Johan
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Phillipson, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Clinical and Experimental Pancreatic Islet Transplantation to Striated Muscle: Establishment of a Vascular System Similar to that in Native Islets2010In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, no 10, p. 2569-2578Article in journal (Refereed)
    Abstract [en]

    Objective: Curing type 1 diabetes by transplanting pancreatic islets into the liver is associated with poor long-term outcome and graft failure at least partly due to inadequate graft revascularization. The aim of the current study was to evaluate striated muscle as a potential angiogenic site for islet transplantation. Research Design and Methods: The current study presents a new experimental model which is found applicable to clinical islet transplantation. Islets were implanted into striated muscle where after intra-islet vascular density and blood flow were visualized with intravital and confocal microscopy in mice, and by magnetic resonance imaging in three auto-transplanted pancreatectomized patients. Mice were rendered neutropenic by repeated injections of Gr-1 antibody and diabetes was induced by alloxan treatment. Results: Contrary to liver-engrafted islets, islets transplanted to mouse muscle were revascularized with vessel densities and blood flow entirely comparable to islets within intact pancreas. Initiation of islet revascularization at the muscular site was dependent on neutrophils, and the function of islets transplanted to muscle was proven by curing diabetic mice. The experimental data were confirmed in auto-transplanted patients where higher plasma volumes were measured in islets engrafted in forearm muscle compared to adjacent muscle tissue through high-resolution magnetic resonance imaging. Conclusions: This study presents a novel paradigm in islet transplantation whereby recruited neutrophils are crucial for the functionally restored intra-islet blood perfusion following transplantation to striated muscle under experimental and clinical situations.

  • 46.
    Ciray, Ipek
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bergh, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Early response of breast cancer bone metastases to chemotherapy evaluated with MR imaging2001In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 42, no 2, p. 198-206Article in journal (Other academic)
    Abstract [en]

    PURPOSE:

    To compare T1-weighted spin-echo and fat-suppressed long echo time inversion recovery turbo spin-echo (long TE IR-TSE) MR images in the evaluation of early response of breast cancer bone metastases to chemotherapy.

    MATERIAL AND METHODS:

    Eighteen breast cancer patients with known bone metastases were investigated prospectively by MR, using T1-weighted and long TE IR-TSE sequences on the sternum, spine, pelvis and proximal femora, before and after a median of 6 courses of chemotherapy. Therapeutic response evaluation with MR was based on change in tumor size assessed quantitatively by measuring all focal metastases, and change in pattern and signal intensity (SI) of the metastases, assessed visually. Combined response evaluation based on clinical findings, conventional radiography, and scintigraphy was used as reference.

    RESULTS:

    Progressive disease (2 patients) and no change (4 patients) were assessed equally well on both MR sequences. Long TE IR-TSE demonstrated partial response with higher accuracy than T1-weighted images, 58% (7/12 patients) vs. 17% (2/12 patients). In patients without progression there was an SI increase in or around the metastases in 6 patients on T1-weighted images and in 7 patients on long TE IR-TSE images.

    CONCLUSION:

    The long TE IR-TSE sequence demonstrated early partial response of breast cancer bone metastases to chemotherapy more accurately than the T1-weighted sequence.

  • 47.
    Covaciu, Lucian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ortiz-Nieto, Francisco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Human brain MR spectroscopy thermometry using metabolite aqueous-solution calibrations2010In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 31, no 4, p. 807-814Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To estimate absolute brain temperature using proton MR spectroscopy ((1)H-MRS) and mean brain-body temperature difference of healthy human volunteers. MATERIALS AND METHODS: Chemical shift difference between temperature-dependent water spectral line position and temperature-stable metabolite spectral reference was used for the estimations of absolute brain temperature. Temperature calibrations constants were obtained from the spectra of the N-acetyl aspartate (NAA line at approximately 2.0 ppm), glycero-phosphocholine (GPC line at approximately 3.2 ppm), and creatine (Cr line at approximately 3.0 ppm) aqueous solutions with pH values within physiologically pertinent ranges. Single-voxel PRESS sequence (TR/TE 2000/80 ms) was used for this purpose. Brain temperature was determined by averaging the temperatures computed from water-Cho, water-Cr, and water-NAA chemical shift differences. RESULTS: The mean brain temperature of 18 healthy volunteers was 38.1 +/- 0.4 degrees C and mean brain-body (rectal) temperature difference was 1.3 +/- 0.4 degrees C. CONCLUSION: Improved accuracy of the temperature constants and averaging the temperatures computed from water-Cho, water-Cr, and water-NAA chemical shift differences increased the reliability of the brain temperature estimations.

  • 48.
    Covaciu, Lucian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bengtsson, Caroline
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Allers, M
    Lunderquist, A
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Brain temperature in volunteers subjected to intranasal cooling2011In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 37, no 8, p. 1277-1284Article in journal (Refereed)
    Abstract [en]

    Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods. Intranasal balloons catheters circulated with saline at 20A degrees C were applied for 60 min in ten awake volunteers. No sedation was used. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects' personal experience were completed after the experiment. Brain temperature decrease measured by MRSI was -1.7 +/- A 0.8A degrees C and by phase-mapping -1.8 +/- A 0.9A degrees C (n = 9) at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 +/- A 0.3A degrees C (n = 5). The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent in the MMSE test. Postcooling nasal examination detected increased nasal secretion in nine of the ten volunteers. Volunteers' acceptance of the method was good. Both MR techniques revealed brain temperature reductions after 60 min of intranasal cooling with balloons circulated with saline at 20A degrees C in awake, unsedated volunteers.

  • 49.
    Covaciu, Lucian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Bengtsson, Caroline
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Allers, Mats
    Division of thoracic sciences, Department of clinical sciences, Lund University.
    Lunderquist, Anders
    Department of radiology, Lund University.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Brain temperature in healthy volunteers subjected to intranasal cooling2011In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 37, no 8, p. 1277-1284Article in journal (Other academic)
    Abstract [en]

    Purpose:

    Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods.

    Methods:

    Intranasal balloons catheters circulated with saline at 20 °C were applied for 60 min in 10 healthy, unsedated volunteers. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects personal experience were filled after the experiment.

    Results:

    Brain temperature decrease measured by MRSI was -1.7 ± 0.8°C and by phase-mapping -1.8 ± 0.9°C at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 ± 0.3°C. The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent at MMSE test. Postcooling nasal examination detected increased nasal secretion in 9 of the 10 volunteers. Volunteer’s acceptance of the method was good.   

    Conclusion:

    Both MR techniques revealed brain temperature reductions after 60 min intranasal cooling with balloons circulated with saline at 20 °C in healthy and unsedated volunteers.

  • 50. Daouacher, Georgios
    et al.
    von Below, Catrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Gestblom, Charlotta
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Grzegorek, Rafael
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Waldén, Mauritz
    Laparoscopic extended pelvic lymph node (LN) dissection as validation of the performance of [(11) C]-acetate positron emission tomography/computer tomography in the detection of LN metastasis in intermediate- and high-risk prostate cancer2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, no 1, p. 77-83Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the accuracy of the radiopharmaceutical [(11) C]-acetate combined with positron emission tomography/computer tomography (acetate-PET/CT) in lymph node (LN) staging in newly diagnosed prostate cancer cases. A second aim was to evaluate the potential discriminative properties of acetate-PET/CT in clinical routine.

    PATIENTS AND METHODS: In a prospective comparative study, from July 2010 to June 2013, 53 men with newly histologically diagnosed intermediate- or high-risk prostate cancer underwent acetate-PET/CT investigation at one regional centre before laparoscopic extended pelvic LN dissection (ePLND) at one referral centre. The sensitivity, specificity and accuracy of acetate-PET/CT were calculated. Comparisons were made between true-positive and false-negative PET/CT cases to identify differences in the clinical parameters: PSA level, Gleason status, lymph metastasis burden and size, calculated risk of LN involvement, and curative treatment decisions.

    RESULTS: In all, 26 patients had surgically/histologically confirmed LN metastasis (LN+). Acetate-PET/CT was true positive in 10 patients, false positive in one, false negative in 16, and true negative in 26. The individual sensitivity was 38%, specificity 96%, and accuracy 68%. The acetate-PET/CT positive cases had significantly more involved LNs (mean 7.9 vs 2.4, P < 0.001) with larger cancer diameters (14.1 vs 4.9 mm, P = 0.001) and fewer eventually had treatment with curative intent (40% vs 94%, P <0.005), although we lack long-term outcome data.

    CONCLUSION: Acetate-PET/CT has too low a sensitivity for routine LN staging but the specificity is high. The acetate-PET/CT positive cases have a very high burden of LN spread.

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