| 1. |
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| 2. |
- Kero, Tanja, et al.
(författare)
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Evaluation of quantitative CMR perfusion imaging by comparison with simultaneous 15O-water-PET
- 2021
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Ingår i: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1071-3581 .- 1532-6551. ; 28, s. 1252-1266
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWe assessed the quantitative accuracy of cardiac perfusion measurements using dynamic contrast-enhanced MRI with simultaneous 15O-water PET as reference with a fully integrated PET-MR scanner.Methods15 patients underwent simultaneous DCE MRI and 15O-water PET scans at rest and adenosine-stress on an integrated PET-MR scanner. Correlation and agreement between MRI- and PET-based global and regional MBF values were assessed using correlation and Bland–Altman analysis.ResultsThree subjects were excluded due to technical problems. Global mean (± SD) MBF values at rest and stress were 0.97 ± 0.27 and 3.19 ± 0.70 mL/g/min for MRI and 1.02 ± 0.28 and 3.13 ± 1.16 mL/g/min for PET (P = 0.66 and P = 0.81). The correlations between global and regional MRI- and PET-based MBF values were strong (r = 0.86 and r = 0.75). The biases were negligible for both global and regional MBF comparisons (0.01 and 0.00 mL/min/g for both), but the limits of agreement were wide for both global and regional MBF, with larger variability for high MBF-values.ConclusionThe correlation between simultaneous MBF measurements with DCE MRI and 15O-water PET measured in an integrated PET-MRI was strong but the agreement was only moderate indicating that MRI-based quantitative MBF measurements is not ready for clinical introduction.
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| 3. |
- Parker, Victoria E. R., et al.
(författare)
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Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes
- 2023
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Ingår i: Nature Metabolism. - : NATURE PORTFOLIO. - 2522-5812. ; 5, s. 2086-2093
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Tidskriftsartikel (refereegranskat)abstract
- Cotadutide is a dual glucagon-like peptide 1 and glucagon receptor agonist under development for the treatment of non-alcoholic steatohepatitis and type 2 diabetes mellitus (T2DM) and chronic kidney disease. Non-alcoholic steatohepatitis is a complex disease with no approved pharmacotherapies, arising from an underlying state of systemic metabolic dysfunction in association with T2DM and obesity. Cotadutide has been shown to improve glycaemic control, body weight, lipids, liver fat, inflammation and fibrosis. We conducted a two-part, randomized phase 2a trial in men and women with overweight or obesity diagnosed with T2DM to evaluate the efficacy and safety of cotadutide compared with placebo and liraglutide. The primary endpoints were change from baseline to day 28 of treatment in postprandial hepatic glycogen (part A) and to day 35 of treatment in fasting hepatic glycogen (part B) with cotadutide versus placebo. Secondary endpoints in part B were changes in fasting hepatic glycogen with cotadutide versus the mono glucagon-like peptide 1 receptor agonist, liraglutide, and change in hepatic fat fraction. The trial met its primary endpoint. We showed that cotadutide promotes greater reductions in liver glycogen and fat compared with placebo and liraglutide. Safety and tolerability findings with cotadutide were comparable to those of previous reports. Thus, this work provides evidence of additional benefits of cotadutide that could be attributed to glucagon receptor engagement. Our results suggest that cotadutide acts on the glucagon receptor in the human liver to promote glycogenolysis and improve the metabolic health of the liver. ClinicalTrials.gov registration: NCT03555994. In a two-part randomized phase 2a trial in men and women with overweight or obesity and type 2 diabetes mellitus, cotadutide promoted greater reductions in liver glycogen and fat than placebo and liraglutide.
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| 17. |
- Ahlstedt, Jonas, et al.
(författare)
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Non-invasive imaging methodologies for assessment of radiation damage to bone marrow and kidneys from peptide receptor radionuclide therapy. : -
- 2019
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 1423-0194 .- 0028-3835. ; 110:1-2, s. 130-138
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Peptide receptor radionuclide therapy (PRRT) is becoming clinical routine for management of neuroendocrine tumours. The number of PRRT cycles is correlated with treatment effect but theoretically limited by off-target radiation damage to kidneys and bone marrow. New imaging biomarkers for assessment of PRRT tissue damage would enable evaluation of novel renal and bone marrow protective agents, as well as personalised PRRT treatment regiments. Methods: Mice treated with [177Lu]Lu-DOTA-TATE PRRT or vehicle were examined at baseline and following treatment with [18F]fluorothymidine (FLT) positron emission tomography (PET) and technetium-99m-mercapto-acetyl-tri-glycine ([99mTc]Tc-Mag3) single-photon emission tomography (SPECT) to assess dynamic changes in bone marrow proliferation and renal function, respectively. Results: Bone marrow proliferation as assessed by [18F]FLT was decreased 2 days after PRRT treatment, but not vehicle, compared to baseline (target-to-background ratio [TBRmax] baseline:1.69 ± 0.29 vs. TBRmax PRRT: 0.91 ± 0.02, p < 0.01). Renal function as assessed by [99mTc]Tc-Mag3 SPECT was similarly decreased 2 days following PRRT compared to vehicle (fractional uptake rate [FUR] vehicle: 0.030 ± 0.014 s–1 vs. FUR PRRT: 0.0051 ± 0.0028 s–1, p < 0.01). Conclusion: [18F]FLT PET and [99mTc]Tc-Mag3 SPECT are promising techniques for assessing bone marrow and renal injury from [177Lu]Lu-DOTA-TATE PRRT and may potentially improve patient management by allowing evaluation of protective interventions as well as enabling personalised PRRT treatments.
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| 18. |
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| 19. |
- Björkman-Burtscher, Isabella, et al.
(författare)
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Quality assessment of localization technique performance in small volume in vivo 1H MR spectroscopy
- 1999
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Ingår i: Magnetic Resonance Imaging. - 1873-5894. ; 17:10, s. 1511-1519
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Tidskriftsartikel (refereegranskat)abstract
- A new phantom and evaluation method for experimental evaluation of 1H-magnetic resonance spectroscopy single volume localization techniques regarding signal contamination (C), defined as the part of the signal originating outside the volume of interest, is presented. The quality assessment method is based on a spherical phantom with an oil/water interface in order to reduce susceptibility effects, and applied for stimulated-echo acquisition method (STEAM) and spin-echo (SE) sequences, echo times of 270, 135, and 10 ms, and cubic volumes of interest (VOI) of 1(3), 1.5(3), 2(3), 2.5(3), and 3(3) cm3. To be able to mimic measurements of the contamination in three dimensions the physical gradients representing the three orthogonal directions for slice selection were shifted in the pulse sequences. Contamination values in one dimension differed between 6.5% and 8.4% in SE sequences, and between 0.7% and 13.8% in STEAM sequences. In STEAM sequences a decrease of C with increasing VOI size was observed while SE sequences showed comparable C values for the different VOI sizes tested. The total contamination in three dimensions were 19% and 18% in SE and STEAM sequences with a TE of 270 ms, and 7% in a STEAM sequence with a TE of 10 ms, respectively. The presented evaluation method is easily applied to the new phantom and showed high reproducibility.
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| 20. |
- Dwibedi, Chinmay Kumar, et al.
(författare)
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Long-range dispersal moved Francisella tularensis into Western Europe from the East
- 2016
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Ingår i: Microbial Genomics. - : Microbiology Society. - 2057-5858. ; 2:12
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Tidskriftsartikel (refereegranskat)abstract
- For many infections transmitting to humans from reservoirs in nature, disease dispersal patterns over space and time are largely unknown. Here, a reversed genomics approach helped us understand disease dispersal and yielded insight into evolution and biological properties of Francisella tularensis, the bacterium causing tularemia. We whole-genome sequenced 67 strains and characterized by single-nucleotide polymorphism assays 138 strains, collected from individuals infected 1947-2012 across Western Europe. We used the data for phylogenetic, population genetic and geographical network analyses. All strains (n= 205) belonged to a monophyletic population of recent ancestry not found outside Western Europe. Most strains (n= 195) throughout the study area were assigned to a star-like phylogenetic pattern indicating that colonization of Western Europe occurred via clonal expansion. In the East of the study area, strains were more diverse, consistent with a founder population spreading from east to west. The relationship of genetic and geographic distance within the F. tularensis population was complex and indicated multiple long-distance dispersal events. Mutation rate estimates based on year of isolation indicated null rates; in outbreak hotspots only, there was a rate of 0.4 mutations/genome/year. Patterns of nucleotide substitution showed marked AT mutational bias suggestive of genetic drift. These results demonstrate that tularemia has moved from east to west in Europe and that F. tularensis has a biology characterized by long-range geographical dispersal events and mostly slow, but variable, replication rates. The results indicate that mutation-driven evolution, a resting survival phase, genetic drift and long-distance geographical dispersal events have interacted to generate genetic diversity within this species.
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| 21. |
- Golman, Klaes, et al.
(författare)
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Cardiac metabolism measured noninvasively by hyperpolarized (13)C MRI.
- 2008
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 59:5, s. 1005-1013
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Tidskriftsartikel (refereegranskat)abstract
- Pyruvate is included in the energy production of the heart muscle and is metabolized into lactate, alanine, and CO(2) in equilibrium with HCO(3) (-). The aim of this study was to evaluate the feasibility of using (13)C hyperpolarization enhanced MRI to monitor pyruvate metabolism in the heart during an ischemic episode. The left circumflex artery of pigs (4 months, male, 29-34 kg) was occluded for 15 or 45 min followed by 2 hr of reperfusion. Pigs were examined by (13)C chemical shift imaging following intravenous injection of 1-(13)C pyruvate. (13)C chemical shift MR imaging was used in order to visualize the local concentrations of the metabolites. After a 15-min occlusion (no infarct) the bicarbonate signal level in the affected area was reduced (25-44%) compared with the normal myocardium. Alanine signal level was normal. After a 45-min occlusion (infarction) the bicarbonate signal was almost absent (0.2-11%) and the alanine signal was reduced (27-51%). Due to image-folding artifacts the data obtained for lactate were inconclusive. These studies demonstrate that cardiac metabolic imaging with hyperpolarized 1-(13)C-pyruvate is feasible. The changes in concentrations of the metabolites within a minute after injection can be detected and metabolic maps constructed. Magn Reson Med 59:1005-1013, 2008. (c) 2008 Wiley-Liss, Inc.
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| 22. |
- Heurling, Kerstin, et al.
(författare)
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Disturbances in brain energy metabolism in insulin resistance and diabetes and Alzheimer's disease — Learnings from brain imaging biomarkers
- 2020
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Ingår i: International Review of Neurobiology. - : Elsevier. - 0074-7742. ; 154, s. 111-130
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Forskningsöversikt (refereegranskat)abstract
- Medical imaging techniques, such as structural and functional magnetic resonance imaging and positron emission tomography, have been used to gain a better understanding of the alterations of the metabolic processes in the brain relating to type 2 diabetes melltius, insulin resistance and Alzheimer's disease. These studies have shown that there are several similarities in the effects that these seemingly disparate diseases have on the brain, and that some of the abnormalities are reversed by metabolic interventions. This review provides an overview of the overlap between these diseases using medical imaging, focusing on glucose metabolism, mitochondrial function and lipid metabolism.
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| 23. |
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| 24. |
- Johansson, Edvin, et al.
(författare)
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Gradient echo imaging of flowing hyperpolarized nuclei : theory and phantom studies on 129Xe dissolved in ethanol
- 2002
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Ingår i: Journal of Magnetic Resonance. - 1090-7807 .- 1096-0856. ; 159:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- The influence of flip angle and flow velocity on the signal intensity achieved when imaging a hyperpolarized substance with a spoiled gradient echo sequence was investigated. The study was performed both theoretically and experimentally using hyperpolarized xenon dissolved in ethanol. Analytical expressions regarding the optimal flip angle with respect to signal and the corresponding signal level are presented and comparisons with thermally polarized substances are made. Both experimentally and theoretically, the optimal flip angle was found to increase with increasing flow velocity. Numerical calculations showed that the velocity dependence of the signal differs between the cases of hyperpolarized and thermally polarized substances.
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| 25. |
- Johansson, Edvin
(författare)
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NMR Imaging of Flow and Perfusion using Hyperpolarized Nuclei: Theoretical Considerations and Application to Experimental Models
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the studies presented in this thesis, hyperpolarized tracers have been used for the study of macroscopic flow and capillary perfusion with magnetic resonance imaging. The feasibility of performing vascular studies using echo-planar imaging (EPI) and hyperpolarized 129Xe was investigated using xenon dissolved in ethanol prior to injection into a flow phantom. It was concluded that hyperpolarized 129Xe could only be expected to yield images of a sufficiently good SNR if depolarization losses and dilution effects could be avoided. Using the same nuclide, the signal equation for the spoiled gradient-echo sequence in the presence of flow was investigated using a similar set-up, and experimental data were compared with derived theoretical expressions. Relationships were also derived for the optimal flip angle at different flow distributions. Two investigations of perfusion with hyperpolarized 13C in labelled compounds were performed. One concern with hyperpolarized tracers is that they depolarize during the course of the perfusion examination. This behaviour was incorporated into the theory of bolus tracking. It was found that no modification of the theory was necessary to quantify tissue blood flow. Assuming an intravascular tracer, it was demonstrated that the blood volume and mean transit time (MTT) were underestimated if the MTT was long or the depolarization rate of the tracer was high. It was also shown, analytically and by simulations, that if the depolarization rate was known, this effect could be compensated for. An experimental investigation using hyperpolarized 13C for the study of cerebral blood flow in rat following venous injection was performed. Maps of the cerebral blood flow, cerebral blood volume and MTT were calculated and the MTT could be evaluated quantitatively (2.8 ± 0.8 s in five animals). A new method of assessing tissue blood flow, denoted bolus differentiation, was also proposed based on the fact that the magnetization of a hyperpolarized tracer can be destroyed permanently by subjecting the tracer to radio-frequency excitation. The technique allows for a tissue blood flow assessment that is insensitive to arterial delay and dispersion and these parameters can be determined as a by-product of the acquired image series. In an experimental investigation in rabbit kidneys, quantitative maps of the cortical blood flow (5.7/5.4 ± 1.6/1.3 ml/min per ml tissue) (mean ± SD, right/left kidney), arterial mean transit time (1.47/1.42 ± 0.07/0.07 s) and arterial dispersion (1.78/1.93 ± 0.40/0.42 s2) were calculated and evaluated in six animals.
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| 26. |
- Johansson, Edvin, et al.
(författare)
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Perfusion assessment with bolus differentiation : a technique applicable to hyperpolarized tracers
- 2004
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 52:5, s. 51-1043
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Tidskriftsartikel (refereegranskat)abstract
- A new technique for assessing tissue blood flow using hyperpolarized tracers, based on the fact that the magnetization of a hyperpolarized substance can be destroyed permanently, is described. Assessments of blood flow with this technique are inherently insensitive to arterial delay and dispersion, and allow for quantification of the transit time and dispersion in the arteries that supply the investigated tissue. Renal cortical blood flow was studied in six rabbits using a 13C-labeled compound (2-hydroxyethylacrylate) that was polarized by the parahydrogen-induced polarization (PHIP) technique. The renal cortical blood flow was estimated to be 5.7/5.4 +/- 1.6/1.3 ml/min per milliliter of tissue (mean +/- SD, right/left kidney), and the mean transit time and dispersion in the renal arteries were determined to be 1.47/1.42 +/- 0.07/0.07 s and 1.78/1.93 +/- 0.40/0.42 s2, respectively.
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| 27. |
- Johansson, Edvin, et al.
(författare)
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Scenario-based trajectory generation and density estimation towards risk analysis of autonomous vehicles
- 2023
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Ingår i: IEEE Conference on Intelligent Transportation Systems, Proceedings, ITSC. ; , s. 1375-1380
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Konferensbidrag (refereegranskat)abstract
- A large amount of testing is needed to determine when autonomous vehicles are sufficiently safe. To achieve this goal, test cases should be representative of real-world driving but also designed to provide sufficient coverage of both frequent and rare events. This is a crucial step in finding potential high consequence events, failure borders of the Autonomous Driving (AD) function and accurate estimation of the corresponding residual risks. In this paper, we propose a new method to adapt generative models to generate vehicle trajectories that are representative of the ones collected from the real world. The method uses Non-Uniform Rational B-Splines (NURBS) combined with normalizing flows to build a statistical scenario model. The method allows us to estimate a joint probability density that can be used to evaluate the likelihood of different trajectory occurrences. We demonstrate the method for statistical modeling on the (smooth and abrupt) cut-in traffic scenario and we give an example of how the estimated joint probability distribution can be used to assess the risk (trajectory occurrence probability and criticality) for different test cases. The results can be used for accelerated testing purposes, where the aim is to sample the rare tests more frequently, but can also be used to calculate the failure probability of AD functions.
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| 28. |
- Karageorgis, Anastassia, et al.
(författare)
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A multi-center preclinical study of gadoxetate DCE-MRI in rats as a biomarker of drug induced inhibition of liver transporter function
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Drug-induced liver injury (Dili) is a leading cause of acute liver failure and transplantation. Dili can be the result of impaired hepatobiliary transporters, with altered bile formation, flow, and subsequent cholestasis. We used gadoxetate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), combined with pharmacokinetic modelling, to measure hepatobiliary transporter function in vivo in rats. The sensitivity and robustness of the method was tested by evaluating the effect of a clinical dose of the antibiotic rifampicin in four different preclinical imaging centers. The mean gadoxetate uptake rate constant for the vehicle groups at all centers was 39.3 +/- 3.4 s -1 (n = 23) and 11.7 +/- 1.3 s -1 (n = 20) for the rifampicin groups. The mean gadoxetate efflux rate constant for the vehicle groups was 1.53 +/- 0.08 s -1 (n = 23) and for the rifampicin treated groups was 0.94 +/- 0.08 s -1 (n = 20). Both the uptake and excretion transporters of gadoxetate were statistically significantly inhibited by the clinical dose of rifampicin at all centers and the size of this treatment group effect was consistent across the centers. Gadoxetate is a clinically approved MRI contrast agent, so this method is readily transferable to the clinic. Conclusion: Rate constants of
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| 29. |
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| 30. |
- Karlsson, Edvin, et al.
(författare)
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Airborne microbial biodiversity and seasonality in Northern and Southern Sweden
- 2020
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Ingår i: PeerJ. - : PeerJ. - 2167-8359. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Microorganisms are essential constituents of ecosystems. To improve our understanding of how various factors shape microbial diversity and composition in nature it is important to study how microorganisms vary in space and time. Factors shaping microbial communities in ground level air have been surveyed in a limited number of studies, indicating that geographic location, season and local climate influence the microbial communities. However, few have surveyed more than one location, at high latitude or continuously over more than a year. We surveyed the airborne microbial communities over two full consecutive years in Kiruna, in the Arctic boreal zone, and Ljungbyhed, in the Southern nemoral zone of Sweden, by using a unique collection of archived air filters. We mapped both geographic and seasonal differences in bacterial and fungal communities and evaluated environmental factors that may contribute to these differences and found that location, season and weather influence the airborne communities. Location had stronger influence on the bacterial community composition compared to season, while location and season had equal influence on the fungal community composition. However, the airborne bacterial and fungal diversity showed overall the same trend over the seasons, regardless of location, with a peak during the warmer parts of the year, except for the fungal seasonal trend in Ljungbyhed, which fluctuated more within season. Interestingly, the diversity and evenness of the airborne communities were generally lower in Ljungbyhed. In addition, both bacterial and fungal communities varied significantly within and between locations, where orders like Rhizobiales, Rhodospirillales and Agaricales dominated in Kiruna, whereas Bacillales, Clostridiales and Sordariales dominated in Ljungbyhed. These differences are a likely reflection of the landscape surrounding the sampling sites where the landscape in Ljungbyhed is more homogenous and predominantly characterized by artificial and agricultural surroundings. Our results further indicate that local landscape, as well as seasonal variation, shapes microbial communities in air.
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| 31. |
- Karlsson, Edvin, et al.
(författare)
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Clonality of erythromycin resistance in Francisella tularensis
- 2016
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 71:10, s. 2815-2823
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We analysed diverse strains of Francisella tularensis subsp. holarctica to assess if its division into biovars I and II is associated with specific mutations previously linked to erythromycin resistance and to determine the distribution of this resistance trait across this subspecies. Methods:Three-hundred and fourteen F. tularensis subsp. holarctica strains were tested for erythromycin susceptibility and whole-genome sequences for these strains were examined for SNPs in genes previously associated with erythromycin resistance. Each strain was assigned to a global phylogenetic framework using genome-wide canonical SNPs. The contribution of a specific SNP to erythromycin resistance was examined using allelic exchange. The geographical distribution of erythromycin-resistant F. tularensis strains was further investigated by literature search. Results:There was a perfect correlation between biovar II strains (erythromycin resistance) and the phylogenetic group B.12. Only B.12 strains had an AaEuroS -> aEuroSC SNP at position 2059 in the three copies of the rrl gene. Introducing 2059C into an rrl gene of an erythromycin-susceptible F. tularensis strain resulted in resistance. An additional 1144 erythromycin-resistant strains were identified from the scientific literature, all of them from Eurasia. Conclusions:Erythromycin resistance in F. tularensis is caused by an A2059C rrl gene mutation, which exhibits a strictly clonal inheritance pattern found only in phylogenetic group B.12. This group is an extremely successful clone, representing the most common type of F. tularensis throughout Eurasia.
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| 32. |
- Karlsson, Edvin, et al.
(författare)
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The phylogeographic pattern of Francisella tularensis in Sweden indicates a Scandinavian origin of Eurosiberian tularaemia
- 2013
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Ingår i: Environmental Microbiology. - : Wiley. - 1462-2912 .- 1462-2920. ; 15:2, s. 634-645
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies of the causative agent of tularaemia, Francisella tularensis have identified phylogeographic patterns suggestive of environmental maintenance reservoirs. To investigate the phylogeography of tularaemia in Sweden, we selected 163 clinical isolates obtained during 1995-2009 in 10 counties and sequenced one isolate's genome to identify new genetic markers. An improved typing scheme based on two indels and nine SNPs was developed using hydrolysis or TaqMan MGB probe assays. The results showed that much of the known global genetic diversity of F. tularensis subsp. holarctica is present in Sweden. Thirteen of the 163 isolates belonged to a new genetic group that is basal to all other known members of the major genetic clade B.I, which is spread across the Eurosiberian region. One hundred and twenty-five of the 163 Swedish isolates belonged to B.I, but individual clades' frequencies differed from county to county (P < 0.001). Subsequent analyses revealed a correlation between genotype variation over time and recurrent outbreaks at specific places, supporting the 'maintenance reservoir' environmental maintenance hypothesis. Most importantly, the findings reveal the presence of diverse source populations of F. tularensis subsp. holarctica in Sweden and suggest a historical spread of the disease from Scandinavia to other parts of Eurosiberia.
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| 33. |
- Lärkeryd, Adrian, et al.
(författare)
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CanSNPer : a hierarchical genotype classifier of clonal pathogens
- 2014
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Ingår i: Bioinformatics. - : Oxford University Press. - 1367-4803 .- 1367-4811. ; 30:12, s. 1762-1764
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Tidskriftsartikel (refereegranskat)abstract
- Advances in typing methodologies have recently reformed the field of molecular epidemiology of pathogens. The falling cost of sequencing technologies is creating a deluge of whole genome sequencing data that burdens bioinformatics resources and tool development. In particular, single nucleotide polymorphisms in core genomes of pathogens are recognized as the most important markers for inferring genetic relationships because they are evolutionarily stable and amenable to high-throughput detection methods. Sequence data will provide an excellent opportunity to extend our understanding of infectious disease when the challenge of extracting knowledge from available sequence resources is met. Here, we present an efficient and user-friendly genotype classification pipeline, CanSNPer, based on an easily expandable database of predefined canonical single nucleotide polymorphisms.
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| 34. |
- Lätt, Jimmy, et al.
(författare)
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In vivo visualization of displacement-distribution-derived parameters in q-space imaging.
- 2008
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Ingår i: Magnetic Resonance Imaging. - : Elsevier BV. - 1873-5894 .- 0730-725X. ; 26:1, s. 77-87
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study aimed to explore the potential of in vivo q-space imaging in the differentiation between different cerebral water components. Materials and Methods Diffusion-weighted imaging was performed in six directions with 32 equally spaced q values and a maximum b value of 6600 s/mm2. The shape of the signal-attenuation curve and the displacement propagator were examined and compared with a normal distribution using the kurtosis parameter. Maps displaying kurtosis, fast and slow components of the apparent diffusion coefficients, fractional anisotropy and directional diffusion were calculated. The displacement propagator was further described by the full width at half and at tenth maximum and by the probability density of zero displacement P(0). Three healthy volunteers and three patients with previously diagnosed multiple sclerosis (MS) were examined. Results Simulations indicated that the kurtosis of a signal-attenuation curve can determine if more than one water component is present and that care must be taken to select an appropriate threshold. It was possible to distinguish MS plaques in both signal and diffusional kurtosis maps, and in one patient, plaques of different degree of demyelinization showed different behavior. Discussion Our results indicate that in vivo q-space analysis is a potential tool for the assessment of different cerebral water components, and it might extend the diagnostic interpretation of data from diffusion magnetic resonance imaging.
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| 35. |
- Magnusson, Peter, et al.
(författare)
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Passive catheter tracking during interventional MRI using hyperpolarized 13C.
- 2007
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 57:6, s. 1140-1147
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Tidskriftsartikel (refereegranskat)abstract
- nterventional procedures in MRI can be performed preclinically using active or passive catheter-tracking methods. A novel passive nonproton technique is suggested that uses a catheter filled with a hyperpolarized C-13 contrast agent. A prototype three-lumen catheter was built with two closed lumens containing a flowing hyperpolarized C-13 contrast agent. Entire-length C-13 catheter projection visualization could be performed in vivo with a catheter SNR of similar to 80, one dual projection frame per similar to 700 ms, and an in-plane resolution of 2 x 2 mm(2) while traveling through the aorta of a pig. The traveling path of the C-13 catheter was visualized after back-projection catheter reconstruction and after image fusion with an anatomical offline proton road map. Catheter length visualization was aided by an oblique planar visualization mode. The high catheter signal demonstrated, together with the entire catheter length visualization and high surrounding soft-tissue contrast, warrants further development into a real-time technique.
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| 36. |
- Martin, Natalia, et al.
(författare)
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Intrinsic Ligand Effect Governing the Catalytic Activity of Pd Oxide Thin Films
- 2014
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Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 4:10, s. 3330-3334
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Tidskriftsartikel (refereegranskat)abstract
- High-pressure X-ray photoelectron spectroscopy, mass spectrometry, and density functional theory calculations have been combined to study methane oxidation over Pd(100). The measurements reveal a high activity when a two-layer PdO(101) oriented film is formed. Although a one-layer PdO(101) film exhibits a similar surface structure, no or very little activity is observed. The calculations show that the presence of an oxygen atom directly below the coordinatively unsaturated Pd atom in the two-layer PdO(101) film is crucial for efficient methane dissociation, demonstrating a ligand effect that may be broadly important in determining the catalytic properties of oxide thin films.
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| 37. |
- Myrtennäs, Kerstin, et al.
(författare)
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Authors' reply
- 2017
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Ingår i: Infection Ecology & Epidemiology. - : Taylor & Francis. - 2000-8686. ; 210:1, s. 84-84
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Tidskriftsartikel (refereegranskat)
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| 38. |
- Myrtennäs, Kerstin, et al.
(författare)
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Introduction and persistence of tularemia in Bulgaria
- 2016
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Ingår i: Infection Ecology & Epidemiology. - : Taylor & Francis Group. - 2000-8686. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Outbreaks of the zoonotic disease tularemia occurred in north-east Bulgaria in the 1960s. Then came 30 years of epidemiological silence until new outbreaks occurred in west Bulgaria in the 1990s. To investigate how bacterial strains of Francisella tularensis causing tularemia in wildlife and humans in the 1960s and the 1990s were related, we explored their genetic diversity.Material and methods: TenF. tularensis genomes from the 1960s (n=3) and the 1990s (n=7) were sequenced, assigned to canonical single-nucleotide polymorphism (canSNP) clades, and compared to reference genomes. We developed four new canSNP polymerase chain reaction (PCR) assays based on the genome sequence information.Results and discussion: The genetic analysis showed that the outbreaks in the 1960s as well as in the 1990s involved multiple clones and new genetic diversity. The smallest genetic difference found between any of the Bulgarian strains was five SNPs between the strains L2 and 81 isolated 43 years apart, indicating that F. tularensis may persist locally over long time periods without causing outbreaks. The existence of genetically highly similar strain-pairs isolated the same year in the same area from different hosts supports a hypothesis of local expansion of clones during outbreaks. Close relationship (two SNPs) was found between one strain isolated 1961 in northeast Bulgaria and one strain isolated 5 years before in USSR. Historical data coinciding with the actual time point describe the introduction of water rats from USSR into the Bulgarian outbreak area, which may explain the close genetic relationship and the origin of the outbreak.Conclusion: Genome analysis of strains from two outbreaks in the 1960s and the 1990s provided valuable information on the genetic diversity and persistence of F. tularensis in Bulgaria.
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| 39. |
- Månsson, Sven, et al.
(författare)
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13C imaging-a new diagnostic platform.
- 2006
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 16:1, s. 57-67
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Tidskriftsartikel (refereegranskat)abstract
- he evolution of magnetic resonance imaging (MRI) has been astounding since the early 1980s, and a broad range of applications has emerged. To date, clinical imaging of nuclei other than protons has been precluded for reasons of sensitivity. However, with the recent development of hyperpolarization techniques, the signal from a given number of nuclei can be increased as much as 100,000 times, sufficient to enable imaging of nonproton nuclei. Technically, imaging of hyperpolarized nuclei offers several unique properties, such as complete lack of background signal and possibility for local and permanent destruction of the signal by means of radio frequency (RF) pulses. These properties allow for improved as well as new techniques within several application areas. Diagnostically, the injected compounds can visualize information about flow, perfusion, excretory function, and metabolic status. In this review article, we explain the concept of hyperpolarization and the techniques to hyperpolarize 13C. An overview of results obtained within angiography, perfusion, and catheter tracking is given, together with a discussion of the particular advantages and limitations. Finally, possible future directions of hyperpolarized 13C MRI are pointed out.
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| 40. |
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| 41. |
- Månsson, Sven, et al.
(författare)
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Quantification of low fat contents: a comparison of MR imaging and spectroscopy methods at 1.5 and 3 T.
- 2012
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Ingår i: Magnetic Resonance Imaging. - : Elsevier BV. - 1873-5894 .- 0730-725X.
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic resonance spectroscopy (MRS) has long been considered the golden standard for non-invasive measurement of tissue fat content. With improved techniques for fat/water separation, imaging has become an alternative to MRS for fat quantification. Several imaging models have been proposed, but their performance relative to MRS at very low fat contents is yet not fully established. In this work, imaging and spectroscopy were compared at 1.5 T and 3 T in phantoms with 0-3% fat fraction (FF). We propose a multispectral model with individual a priori R(2) relaxation rates for water and fat, and a common unknown R(2)' relaxation. Magnitude and complex image reconstructions were also compared. Best accuracy was obtained with the imaging method at 1.5 T. At 3 T, the FFs were underestimated due to larger fat-water phase shifts. Agreement between measured and true FF was excellent for the imaging method at 1.5 T (imaging: FF(meas)=0.98 FF(true)-0.01%, spectroscopy: FF(meas)=0.77 FF(true)+0.08%), and fair at 3 T (imaging: FF(meas)=0.91 FF(true)-0.19%, spectroscopy: FF(meas)=0.79 FF(true)+0.02%). The imaging method was able to quantify FFs down to approx. 0.5%. We conclude that the suggested imaging model is capable of fat quantification with accuracy and precision similar to or better than spectroscopy and offers an improvement vs. a model with a common R(2)* relaxation only.
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| 42. |
- Oldgren, Jonas, 1964-, et al.
(författare)
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Effects of 6 weeks of treatment with dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes : A randomized, placebo-controlled, exploratory study
- 2021
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Ingår i: Diabetes, obesity and metabolism. - : John Wiley & Sons. - 1462-8902 .- 1463-1326. ; 23:7, s. 1505-1517
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Tidskriftsartikel (refereegranskat)abstract
- Aim To explore the early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure. Materials and Methods Patients with type 2 diabetes on metformin treatment were randomized to double-blind, 6-week placebo or dapagliflozin 10 mg daily treatment. Investigations included cardiac function and structure with myocardial resonance imaging; cardiac oxygen consumption, perfusion and efficiency with [C-11]-acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [F-18]-6-thia-heptadecanoic acid PET, analysed by ANCOVA as least square means with 95% confidence intervals. Results Evaluable patients (placebo: n = 24, dapagliflozin: n = 25; 53% males) had a mean age of 64.4 years, a body mass index of 30.2 kg/m(2) and an HbA1c of 6.7%. Body weight and HbA1c were significantly decreased by dapagliflozin versus placebo. Dapagliflozin had no effect on myocardial efficiency, but external left ventricular (LV) work (-0.095 [-0.145, -0.043] J/g/min) and LV oxygen consumption were significantly reduced (-0.30 [-0.49, -0.12] J/g/min) by dapagliflozin, although the changes were not statistically significant versus changes in the placebo group. Change in left atrial maximal volume with dapagliflozin versus placebo was -3.19 (-6.32, -0.07) mL/m(2) (p = .056). Peak global radial strain decreased with dapagliflozin versus placebo (-3.92% [-7.57%, -0.28%]; p = .035), while peak global longitudinal and circumferential strains were unchanged. Hepatic fatty acid uptake was increased by dapagliflozin versus placebo (0.024 [0.004, 0.044] mu mol/g/min; p = .018), while cardiac uptake was unchanged. Conclusions This exploratory study indicates reduced heart work but limited effects on myocardial function, efficiency and cardiac fatty acid uptake, while hepatic fatty acid uptake increased, after 6 weeks of treatment with dapagliflozin.
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| 43. |
- Polesie, Sam, et al.
(författare)
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Can Dermoscopy Be Used to Predict if a Melanoma Is In Situ or Invasive?
- 2021
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Ingår i: Dermatology Practical & Conceptual. - : Mattioli1885. - 2160-9381. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: The preoperative prediction of whether melanomas are invasive or in situ can influence initial management. Objectives: This study evaluated the accuracy rate, interobserver concordance, sensitivity and specificity in determining if a melanoma is invasive or in situ, as well as the ability to predict invasive melanoma thickness based on clinical and dermoscopic images. Methods: In this retrospective, single-center investigation, 7 dermatologists independently reviewed clinical and dermoscopic images of melanomas to predict if they were invasive or in situ and, if invasive, their Breslow thickness. Fleiss' and Cohen's kappa (kappa) were used for interobserver concordance and agreement with histopathological diagnosis. Results: We included 184 melanomas (110 invasive and 74 in situ). Diagnostic accuracy ranged from 67.4% to 76.1%. Accuracy rates for in situ and invasive melanomas were 57.5% (95% confidence interval [I], 53.1%-61.8%) and 81.7% (95% CI, 78.8%-84.4%), respectively. Interobserver concordance was moderate (kappa = 0.47; 95% CI, 0.44-0.51). Sensitivity for predicting invasiveness ranged from 63.6% to 91.8% for 7 observers, while specificity was 32.4%-82.4%. For all correctly predicted invasive melanomas, agreement between predictions and correct thickness over or under 1.0 mm was moderate (kappa = 0.52; 95% CI, 0.45-0.58). All invasive melanomas incorrectly predicted by any observer as in situ had a thickness <1.0 mm. All 32 melanomas >1.0 mm were correctly predicted to be invasive by all observers. Conclusions: Accuracy rates for predicting thick melanomas were excellent, melanomas inaccurately predicted as in situ were all thin, and interobserver concordance for predicting in situ or invasive melanomas was moderate. Preoperative dermoscopy of suspected melanomas is recommended for choosing appropriate surgical margins.
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| 44. |
- Rullik, Lisa, et al.
(författare)
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Surface oxide development on aluminum alloy 6063 during heat treatment
- 2019
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Ingår i: Surface and Interface Analysis. - : Wiley. - 0142-2421 .- 1096-9918. ; 51:12, s. 1214-1224
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Tidskriftsartikel (refereegranskat)abstract
- We report on the influence of oxygen partial pressure for the development of surface oxides covering the industrial aluminum alloy standard 6063 at temperatures ranging from room temperature to 500° C. Using an array of synchrotron-based techniques, we followed the change in oxide thickness, chemical composition, and the lateral distribution of alloying elements. The impact of the oxygen chemical potential is most visible at high temperatures where the oxide composition changes from mostly Al based to mostly Mg based. This is in stark contrast to the ultra-high vacuum (UHV) conditions where only a partial compositional transition is observed. The microscopy data demonstrate that in the UHV case, Mg segregation onto the surface occurs firstly at grain boundaries at 300° C and secondly at sites over the entire surface at 400° C. Further, the initial oxide thickness is 45 Å, as determined by XPS and XRR, decreases in all observed cases after heating to 300° C. At higher temperatures, however, the oxygen partial pressure highly influences the resulting oxide thickness as evident from our X-ray reflectivity data.
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| 45. |
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| 46. |
- Zare, Aman, et al.
(författare)
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The gut microbiome participates in transgenerational inheritance of low temperature responses in Drosophila melanogaster
- 2018
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Ingår i: FEBS Letters. - : John Wiley & Sons. - 0014-5793 .- 1873-3468. ; 592:24, s. 4078-4086
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Tidskriftsartikel (refereegranskat)abstract
- Environmental perturbations induce transcriptional changes, some of which may be inherited even in the absence of the initial stimulus. Previous studies have focused on transfers through the germ-line although microbiota is also passed on to the offspring. Thus, we inspected the involvement of the gut microbiome in transgenerational inheritance of environmental exposures in Drosophila melanogaster. We grew flies in the cold versus control temperatures and compared their transcriptional patterns in both conditions as well as in their offspring. F2 flies grew in control temperature while we controlled their microbiota acquisition from either F1 sets. Transcriptional status of some genes was conserved transgenerationally, and a subset of these genes, mainly expressed in the gut, was transcriptionally dependent on the acquired microbiome. This article is protected by copyright. All rights reserved.
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| 47. |
- Aad, G., et al.
(författare)
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- 2016
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Ingår i: The European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6052. ; 76:1
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Tidskriftsartikel (refereegranskat)
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| 48. |
- Aad, G., et al.
(författare)
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- 2015
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Tidskriftsartikel (refereegranskat)
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| 49. |
- Aad, G., et al.
(författare)
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- 2015
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Tidskriftsartikel (refereegranskat)
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| 50. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: The European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6052. ; 75:9
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Tidskriftsartikel (refereegranskat)
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