| 1. |
- Lejonklou, Margareta Halin, 1966-, et al.
(författare)
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Effects of Low-Dose Developmental Bisphenol A Exposure on Metabolic Parameters and Gene Expression in Male and Female Fischer 344 Rat Offspring.
- 2017
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Ingår i: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 125:6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bisphenol A (BPA) is an endocrine-disrupting chemical that may contribute to development of obesity and metabolic disorders. Humans are constantly exposed to low concentrations of BPA, and studies support that the developmental period is particularly sensitive.OBJECTIVES: The aim was to investigate the effects of low-dose developmental BPA exposure on metabolic parameters in male and female Fischer 344 (F344) rat offspring.METHODS: Pregnant F344 rats were exposed to BPA via their drinking water, corresponding to (BPA0.5; ) or (BPA50; ), from gestational day (GD) 3.5 until postnatal day (PND) 22, and controls were given vehicle (). Body weight (BW), adipose tissue, liver (weight, histology, and gene expression), heart weight, and lipid profile were investigated in the 5-wk-old offspring.RESULTS: Males and females exhibited differential susceptibility to the different doses of BPA. Developmental BPA exposure increased plasma triglyceride levels ( compared with , females BPA50 ; compared with , males BPA0.5 ) in F344 rat offspring compared with controls. BPA exposure also increased adipocyte cell density by 122% in inguinal white adipose tissue (iWAT) of female offspring exposed to BPA0.5 compared with controls ( number of adipocytes/HPF compared with number of adipocytes/HPF; ) and by 123% in BPA0.5 females compared with BPA50 animals ( number of adipocytes/high power field (HPF) compared with number of adipocytes/HPF; ). In iWAT of male offspring, adipocyte cell density was increased by 129% in BPA50-exposed animals compared with BPA0.5-exposed animals ( number of adipocytes/HPF compared with number of adipocytes/HPF; ). Furthermore, the expression of genes involved in lipid and adipocyte homeostasis was significantly different between exposed animals and controls depending on the tissue, dose, and sex.CONCLUSIONS: Developmental exposure to of BPA, which is 8-10 times lower than the current preliminary EFSA (European Food Safety Authority) tolerable daily intake (TDI) of and is within the range of environmentally relevant levels, was associated with sex-specific differences in the expression of genes in adipose tissue plasma triglyceride levels in males and adipocyte cell density in females when F344 rat offspring of dams exposed to BPA at were compared with the offspring of unexposed controls.
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| 2. |
- Ahlgren, André, et al.
(författare)
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A linear mixed perfusion model for tissue partial volume correction of perfusion estimates in dynamic susceptibility contrast MRI: : Impact on absolute quantification, repeatability, and agreement with pseudo-continuous arterial spin labeling
- 2017
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 77:6, s. 2203-2214
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The partial volume effect (PVE) is an important source of bias in brain perfusion measurements. The impact of tissue PVEs in perfusion measurements with dynamic susceptibility contrast MRI (DSC-MRI) has not yet been well established. The purpose of this study was to suggest a partial volume correction (PVC) approach for DSC-MRI and to study how PVC affects DSC-MRI perfusion results.METHODS: A linear mixed perfusion model for DSC-MRI was derived and evaluated by way of simulations. Twenty healthy volunteers were scanned twice, including DSC-MRI, arterial spin labeling (ASL), and partial volume measurements. Two different algorithms for PVC were employed and assessed.RESULTS: Simulations showed that the derived model had a tendency to overestimate perfusion values in voxels with high fractions of cerebrospinal fluid. PVC reduced the tissue volume dependence of DSC-MRI perfusion values from 44.4% to 4.2% in gray matter and from 55.3% to 14.2% in white matter. One PVC method significantly improved the voxel-wise repeatability, but PVC did not improve the spatial agreement between DSC-MRI and ASL perfusion maps.CONCLUSION: Significant PVEs were found for DSC-MRI perfusion estimates, and PVC successfully reduced those effects. The findings suggest that PVC might be an important consideration for DSC-MRI applications. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.
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| 3. |
- Deh, Kofi, et al.
(författare)
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Multicenter reproducibility of quantitative susceptibility mapping in a gadolinium phantom using MEDI+0 automatic zero referencing
- 2019
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 81:2, s. 1229-1236
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To determine the reproducibility of quantitative susceptibility mapping at multiple sites on clinical and preclinical scanners (1.5 T, 3 T, 7 T, and 9.4 T) from different vendors (Siemens, GE, Philips, and Bruker) for standardization of multicenter studies. Methods: Seven phantoms distributed from the core site, each containing 5 compartments with gadolinium solutions with fixed concentrations between 0.625 mM and 10 mM. Multi-echo gradient echo scans were performed at 1.5 T, 3 T, 7 T, and 9.4 T on 12 clinical and 3 preclinical scanners. DICOM images from the scans were processed into quantitative susceptibility maps using the Laplacian boundary value (LBV) and MEDI+0 automatic uniform reference algorithm. Region of interest (ROI) analyses were performed by a physicist to determine agreement between results from all sites. Measurement reproducibility was assessed using regression, Bland-Altman plots, and the intra-class correlation coefficient (ICC). Results: Quantitative susceptibility mapping (QSM) from all scanners had similar, artifact-free visual appearance. Regression analysis showed a linear relationship between gadolinium concentrations and average QSM measurements for all phantoms (y = 350x – 0.0346, r2>0.99). The SD of measurements increased almost linearly from 32 ppb to 230 ppb as the measured susceptibility increased from 0.26 ppm to 3.56 ppm. A Bland-Altman plot showed the bias, upper, and lower limits of agreement for all comparisons were −10, −210, and 200 ppb, respectively. The ICC was 0.991 with a 95% CI (0.973, 0.99). Conclusions: QSM shows excellent multicenter reproducibility for a large range of susceptibility values encountered in cranial and extra-cranial applications on a diverse set of scanner platforms.
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| 4. |
- Knutsson, Linda, et al.
(författare)
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Arterial Input Function : A Friend or Foe?
- 2023. - 1
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Ingår i: Quantitative Perfusion MRI : Techniques, Applications and Practical Considerations - Techniques, Applications and Practical Considerations. - 9780323952101 - 9780323952095 ; 11, s. 171-196
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Bokkapitel (refereegranskat)
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| 5. |
- Knutsson, Linda, et al.
(författare)
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Dynamic Susceptibility Contrast MRI at 7 T:Tail-Scaling Analysis and Inferences About Field Strength Dependence
- 2017
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Ingår i: Tomography : a journal for imaging research. - : MDPI AG. - 2379-1381. ; 3:2, s. 8-74
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Tidskriftsartikel (refereegranskat)abstract
- Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) following bolus injection of gadolinium contrast agent (CA) is widely used for the estimation of brain perfusion parameters such as cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) for both clinical and research purposes. Although it is predicted that DSC-MRI will have superior performance at high magnetic field strengths, to the best of our knowledge, there are no reports of 7 T DSC-MRI in the literature. It is plausible that the transfer of DSC-MRI to 7 T may be accompanied by increased R2* relaxivity in tissue and a larger difference in ΔR2*-versus-concentration relationships between tissue and large vessels. If not accounted for, this will subsequently result in apparent CBV and CBF estimates that are higher than those reported previously at lower field strengths. The aims of this study were therefore to assess the feasibility of 7 T DSC-MRI and to investigate the apparent field-strength dependence of CBV and CBF estimates. In total, 8 healthy volunteers were examined using DSC-MRI at 7 T. A reduced CA dose of 0.05 mmol/kg was administered to decrease susceptibility artifacts. CBV, CBF, and MTT maps were calculated using standard DSC-MRI tracer-kinetic theory. Subject-specific arterial partial volume correction factors were obtained using a tail-scaling approach. Compared with literature values obtained using the tail-scaling approach at 1.5 T and 3 T, the CBV and CBF values of the present study were found to be further overestimated. This observation is potentially related to an inferred field-strength dependence of transverse relaxivities, although issues related to the CA dose must also be considered.
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| 6. |
- Knutsson, Linda, et al.
(författare)
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Dynamic susceptibility contrast MRI with a prebolus contrast agent administration design for improved absolute quantification of perfusion.
- 2014
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 72:4, s. 996-1006
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Tidskriftsartikel (refereegranskat)abstract
- Arterial partial-volume effects (PVEs) often hamper reproducible absolute quantification of cerebral blood flow (CBF) and cerebral blood volume (CBV) obtained by dynamic susceptibility contrast MRI (DSC-MRI). The aim of this study was to examine whether arterial PVEs in DSC-MRI data can be minimized by rescaling the arterial input function (AIF) using a sagittal-sinus venous output function obtained following a prebolus administration of a low dose of contrast agent.
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| 7. |
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| 8. |
- Kämpe, Robin, et al.
(författare)
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Quantification of normal cerebral oxygen extraction and oxygen metabolism by phase-based MRI susceptometry: evaluation of repeatability using two different imaging protocols.
- 2017
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961. ; 37:2, s. 220-2011
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Tidskriftsartikel (refereegranskat)abstract
- Global oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2 ) were quantified in a test-retest study. Cerebral blood flow (CBF) data, required for CMRO2 estimation, were obtained using dynamic susceptibility contrast MRI (DSC-MRI). OEF and CMRO2 were quantified using two separate data sets, that is, conventional high-resolution (HR) gradient echo (GRE) phase maps as well as echo planar imaging (EPI) phase maps taken from the baseline (precontrast) part of the DSC-MRI time series. The EPI phase data were included to elucidate whether an extra HR-GRE scan is needed to obtain information about OEF and CMRO2 , or if this information can be extracted from the DSC-MRI experiment only.
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| 9. |
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| 10. |
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| 11. |
- Lind, Emelie, et al.
(författare)
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Assessment of MRI contrast agent concentration by quantitative susceptibility mapping (QSM) : application to estimation of cerebral blood volume during steady state
- 2017
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Ingår i: Magnetic Resonance Materials in Physics, Biology, and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661. ; 30:6, s. 555-566
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Tidskriftsartikel (refereegranskat)abstract
- Objective: One major issue in dynamic susceptibility contrast MRI (DSC-MRI) is to accurately determine contrast agent (CA) concentration, since T2* relaxivity in vivo is generally unknown and varies between blood and tissue. In this study, quantitative susceptibility mapping (QSM) was used for quantification of CA concentration. Materials and methods: A DSC-MRI protocol, including phase data acquisition, was applied to 20 healthy volunteers in a test–retest study. By selecting a CSF reference region of interest (ROI), the values of all QSM images were shifted to show no CA-induced change in CSF. CA concentration and cerebral blood volume (CBV) were estimated using shifted QSM data. CSF reference ROI optimization was evaluated by investigation of CBV repeatability. The CBV age dependence was analysed and tissue T2* relaxivity was estimated. Results: The best repeatability of CBV, using an optimal CSF reference ROI, showed test-versus-retest correlations of r = 0.81 and r = 0.91 for white and grey matter, respectively. A slight CBV decrease with age was observed, and the estimated in vivo T2* relaxivity was 85 mM−1s−1. Conclusion: Provided that a carefully selected CSF reference ROI is used to shift QSM image values, susceptibility information can be used to estimate concentration of contrast agent and to calculate CBV.
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| 12. |
- Lind, Emelie, et al.
(författare)
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Dynamic contrast-enhanced QSM for perfusion imaging : a systematic comparison of ΔR2*- and QSM-based contrast agent concentration time curves in blood and tissue
- 2020
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Ingår i: Magnetic Resonance Materials in Physics, Biology, and Medicine. - : Springer Science and Business Media LLC. - 1352-8661 .- 0968-5243. ; 33:5, s. 663-676
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In dynamic susceptibility contrast MRI (DSC-MRI), an arterial input function (AIF) is required to quantify perfusion. However, estimation of the concentration of contrast agent (CA) from magnitude MRI signal data is challenging. A reasonable alternative would be to quantify CA concentration using quantitative susceptibility mapping (QSM), as the CA alters the magnetic susceptibility in proportion to its concentration.MATERIAL AND METHODS: AIFs with reasonable appearance, selected on the basis of conventional criteria related to timing, shape, and peak concentration, were registered from both ΔR2* and QSM images and mutually compared by visual inspection. Both ΔR2*- and QSM-based AIFs were used for perfusion calculations based on tissue concentration data from ΔR2*as well as QSM images.RESULTS: AIFs based on ΔR2* and QSM data showed very similar shapes and the estimated cerebral blood flow values and mean transit times were similar. Analysis of corresponding ΔR2* versus QSM-based concentration estimates yielded a transverse relaxivity estimate of 89 s-1 mM-1, for voxels identified as useful AIF candidate in ΔR2* images according to the conventional criteria.DISCUSSION: Interestingly, arterial concentration time curves based on ΔR2* versus QSM data, for a standard DSC-MRI experiment, were generally very similar in shape, and the relaxivity obtained in voxels representing blood was similar to tissue relaxivity obtained in previous studies.
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| 13. |
- Lind, Emelie
(författare)
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MRI Perfusion Measurements using Magnetic Susceptibility Effects: : Calibration Approaches and Contrast Agent Quantification
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Exchange of oxygen and nutrients between blood and tissue occurs at the capillary level of the blood system. The blood volume flow rate in the capillaries is often referred to as perfusion, and knowledge about perfusion provides important information about the function and viability of the tissue, for example, in patients with ischaemic stroke, cancer, and neurodegenerative diseases.Dynamic susceptibility contrast magnetic resonance imaging (DSC–MRI) is the basic data collection approach used to obtain perfusion information from the studies reported in this doctoral thesis. The approach shows the advantage of providing estimates of not only brain perfusion, or cerebral blood flow (CBF), but also cerebral blood volume (CBV) and mean transit time (MTT). All of these parameters are required for a comprehensive description of microcirculation. When using standard implementations of DSC–MRI image acquisition and post-processing routines, the CBF and CBV values are often overestimated. In DSC–MRI, a contrast agent (CA) bolus is injected intravenously in an arm vein and is subsequently tracked by rapid imaging when passing through the brain. To calculate CBF, CBV, and MTT, CA concentration information from both tissue and blood is required. The main problem of DSC–MRI is estimating reliable CA concentration levels in tissue and artery simultaneously. Relatedly, if transverse relaxivity-based information is used, then the response to the CA, in terms of the change in relaxation rate, ΔR2∗, differs between blood and tissue. Additionally, there is a non-linear dependence on CA concentration in whole blood. Another issue related to estimations of blood concentration is the practical difficulty of finding a voxel containing only blood, implying that the concentration time curve representing blood will be affected by the surrounding tissue, possibly influencing both the shape of the curve and the absolute levels of estimated concentrations. One approach is to obtain CBV estimates with alternative methods, where contrast agent concentration is quantified using the longitudinal relaxation time, T1, or by using a special MRI pulse sequence designed to study the blood contribution to the MRI signal. The information from these additional CBV estimates is used to calibrate the conventional DSC–MRI data. This approach provided perfusion results with the expected absolute levels but showed moderate repeatability and low correlation with arterial spin labelling (ASL), used as a reference perfusion imaging method. Another study included in the context of this doctoral thesis dealt with the issue of partial-volume effects in the voxel selected to represent blood. By rescaling the area under the curve (AUC) of the concentration-versus-time curve measured in an artery (assumed to show the desired shape), with the AUC of a large vein, measured under circumstances more favourable for blood-data registration, CBF and CBV values were calibrated. This method aims primarily to correct for partial volume effects in the blood voxel (i.e. it does not directly address relaxivity issues). An observation of interest in this context was that absolute perfusion levels similar to what was expected from literature data were obtained. Furthermore, the repeatability was more promising using this approach, compared to the ones described above. The phase of the MRI signal is related to the magnetic field strength, which, in turn, is related to the magnetic susceptibility. As the CA alters the magnetic susceptibility, it should, in principle, be possible to obtain information about CA concentration using MRI phase information. This approach was used in three of the studies described in this thesis, for calculation of perfusionrelated parameters in relative and absolute terms. These studies indicated that information about (or related to) magnetic susceptibility is a promising method for estimating CA concentration, whereas a number of methodological issues still need to be resolved or further investigated. It was also shown that the shape of an arterial ΔR2* curve, based on DSC–MRI data, displayed a shape similar to the corresponding curve obtained by using magnetic susceptibility information for assessment of concentration. Thus, the shape of a typical arterial blood concentration curve used in a standard DSC–MRI experiment can probably be regarded reasonably reliable. However, the AUC is likely to be underestimated because of partial-volume effects.
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| 14. |
- Lind, Tania K., et al.
(författare)
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Effects of ethylene oxide chain length on crystallization of polysorbate 80 and its related compounds
- 2021
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 592, s. 468-484
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Tidskriftsartikel (refereegranskat)abstract
- As a result of the synthesis protocol polyoxyethylene sorbitan monooleate (polysorbate 80, PS80) is a highly complex mixture of compounds. PS80 was therefore separated into its main constituents, e.g. polyoxyethylene isosorbide esters and polyoxyethylene esters, as well as mono- di- and polyesters using preparative high-performance liquid chromatography. In this comprehensive study the individual components and their ethoxylation level were verified by matrix assisted laser desorption/ionization time-of-flight and their thermotropic behavior was analyzed using differential scanning calorimetry and X-ray diffraction. A distinct correlation was found between the average length of the ethylene oxide (EO) chains in the headgroup and the individual compounds' ability to crystallize. Importantly, a critical number of EO units required for crystallization of the headgroup was determined (6 EO units per chain or 24 per molecule). The investigation also revealed that the hydrocarbon tails only crystallize for polyoxyethylene sorbitan esters if saturated. PS80 is synthesized by reacting with approximately 20 mol of EO per mole of sorbitol, however, the number of EO units in the sorbitan ester in commercial PS80 products is higher than the expected 20 (5 EO units per chain). The complex behavior of all tested compounds revealed that if the amount of several of the linear by-products is reduced, the number of EO units in the chains will stay below the critical number and the product will not be able to crystallize by the EO chains.
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| 15. |
- Lind, Ulrika, et al.
(författare)
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Analysis of aquaporins from the euryhaline barnacle Balanus improvisus reveals differential expression in response to changes in salinity
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Barnacles are sessile macro-invertebrates, found along rocky shores in coastal areas worldwide. The euryhaline bay barnacle Balanus improvisus (Darwin, 1854) (= Amphibalanus improvisus) can tolerate a wide range of salinities, but the molecular mechanisms underlying the osmoregulatory capacity of this truly brackish species are not well understood. Aquaporins are pore-forming integral membrane proteins that facilitate transport of water, small solutes and ions through cellular membranes, and that have been shown to be important for osmoregulation in many organisms. The knowledge of the function of aquaporins in crustaceans is, however, limited and nothing is known about them in barnacles. We here present the repertoire of aquaporins from a thecostracan crustacean, the barnacle B. improvisus, based on genome and transcriptome sequencing. Our analyses reveal that B. improvisus contains eight genes for aquaporins. Phylogenetic analysis showed that they represented members of the classical water aquaporins (Aqp1, Aqp2), the aquaglyceroporins (Glp1, Glp2), the unorthodox aquaporin (Aqp12) and the arthropod-specific big brain aquaporin (Bib). Interestingly, we also found two big brain-like proteins (BibL1 and BibL2) constituting a new group of aquaporins not yet described in arthropods. In addition, we found that the two water-specific aquaporins were expressed as C-terminal splice variants. Heterologous expression of some of the aquaporins followed by functional characterization showed that Aqp1 transported water and Glp2 water and glycerol, agreeing with the predictions of substrate specificity based on 3D modeling and phylogeny. To investigate a possible role for the B. improvisus aquaporins in osmoregulation, mRNA expression changes in adult barnacles were analysed after long-term acclimation to different salinities. The most pronounced expression difference was seen for AQP1 with a substantial (>100-fold) decrease in the mantle tissue in low salinity (3 PSU) compared to high salinity (33 PSU). Our study provides a base for future mechanistic studies on the role of aquaporins in osmoregulation. © 2017 Lind et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 16. |
- Lundberg, Anna, et al.
(författare)
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Comparison of MRI methods for measuring whole-brain oxygen extraction fraction under different geometric conditions at 7T
- 2022
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Ingår i: Journal of Neuroimaging. - : Wiley. - 1051-2284 .- 1552-6569. ; 32:3, s. 442-458
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Cerebral tissue oxygenation is a critical brain viability parameter, and the magnetic properties of hemoglobin offer the opportunity to noninvasively quantify oxygen extraction fraction (OEF) by magnetic resonance imaging (MRI). Ultrahigh-field MRI shows advantages such as increased sensitivity to magnetic susceptibility differences and improved signal-to-noise ratio that can be translated into smaller voxel size, but also increased sensitivity to static and B1 field inhomogeneities. The aim was to produce a systematic comparison of three MRI-based methods for estimation of OEF.Methods: OEF estimates in 16 healthy subjects were obtained at 7T utilizingsusceptometry-based oximetry (SBO), quantitative susceptibility mapping (QSM), and transverse relaxation rate (R2*). Two major draining veins, that is, the superior sagittal sinus (SSS) and the straight sinus (SS), were investigated, including mutual agreement between the methods in each of the two different vessels, agreement between vessels as well as potential vessel angle and vessel size dependences.Results: Very good correlation (r = .88) was found between SBO-based and QSM-based OEF estimates in SSS. Only QSM showed a moderate correlation (r = .61) between corresponding OEF estimates in SSS and SS. For SBO, a trend of increasing OEF estimates was observed as the SS vessel angle relative to the main magnetic field increased. No obvious size dependence could be established for anymethod. TheR2*-basedOEFestimates were reasonable (35%-36%), but the observed range was somewhat low.Conclusion: The results indicate thatQSMis a promising candidate for assessment of OEF estimates, for example, providing reasonably robust estimates across awide range of vessel orientations.
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| 17. |
- Lundberg, Anna, et al.
(författare)
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Notes on quantitative susceptibility mapping reconstruction accuracy under challenging conditions: Phantom measurements and simulations
- 2022
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Ingår i: Journal of Medical and Scientific Research. ; 10:3, s. 111-117
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic susceptibility can be assessed by quantitative susceptibility mapping (QSM), based on measured magnetic resonance imaging (MRI) phase data. The QSM reconstruction process is, however, mathematically challenging and still not fully robust. A signal-generating holmium [Ho(III)] aqueous solution with air-equivalent magnetic susceptibility was prepared, and used as a surrounding medium in a water phantom with tubes filled with a solution of gadolinium contrast agent at various concentrations. Extended analyses under controlled conditions were accomplished by simulations of the phantom construction. Without surrounding holmium solution, a gadolinium tube positioned centrally, parallel with B0, showed a susceptibility difference that agreed well with theoretical values, whereas a peripheral parallel tube position showed larger deviation. Orientation perpendicular to B0 resulted in less variation between the internal tube positions. Air-equivalent magnetic susceptibility corresponded to 16.5 mM Ho(III) solution. With surrounding holmium solution, several post-processing steps became challenging. Simulations indicated higher degree of underestimation when the theoretical susceptibility difference increased. Details in the mathematical implementation, for example, background field removal can strongly influence the result. Simulated results were, in part, unexpected, and provided awareness of limitations in the reconstruction technique, mainly related to conditions with large susceptibility differences between compartments.
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| 18. |
- Nilsson, Emelie J., et al.
(författare)
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Mechanisms of crystallisation in polysorbates and sorbitan esters
- 2020
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Ingår i: CrystEngComm. - : Royal Society of Chemistry. - 1466-8033. ; 22:22, s. 3840-3853
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Tidskriftsartikel (refereegranskat)abstract
- Polysorbates (PS), commonly known as Tween (TM), are some of the most extensively used excipients and protein stabilisers in biopharmaceutical products worldwide. It is stipulated in the pharmacopoeia specifications that these ethoxylated surfactants are complex mixtures comprised of a wealth of molecular species. While little is known about the propensity of PSs to crystallise, they are used in applications ranging from food products, cosmetics, different types of drug dosage forms like creams and oral products to parenteral applications. However, in recent years a range of issues and safety concerns have appeared when using them for stabilising biopharmaceutical products including precipitation, particle formation, and adverse biological effects. Therefore, the aim of this study was to thoroughly characterise the thermotropic behaviour and mechanism of crystallisation of polysorbates with different hydrocarbon tails and their non-ethoxylated sorbitan ester equivalents for comparison. A systematic and comprehensive product characterisation was carried out, taking advantage of a combination of complementary techniques such as differential scanning calorimetry, matrix assisted laser desorption ionisation time-of-flight and small- and wide-angle X-ray diffraction. We show that polysorbate 80, having an unsaturated hydrocarbon tail, crystallises by the ethylene oxide chains in the headgroup. Polysorbate 20, 40, and 60, containing saturated hydrocarbon esters tails, crystallise not only by the ethylene oxide chains but also by their hydrocarbon tails. An analogous behaviour was observed for the PS non-ethoxylated equivalents, the sorbitan esters. Sorbitan esters with saturated hydrocarbon tails displayed a crystallisation of the tail upon cooling, whereas the sorbitan ester with unsaturated hydrocarbon tail displayed no crystallisation.
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| 19. |
- Olsson, Emma, et al.
(författare)
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MRI-Based Quantification of Magnetic Susceptibility in Gel Phantoms : Assessment of Measurement and Calculation Accuracy
- 2018
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Ingår i: Radiology research and practice. - : Hindawi Limited. - 2090-1941 .- 2090-195X. ; 2018
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Tidskriftsartikel (refereegranskat)abstract
- The local magnetic field inside and around an object in a magnetic resonance imaging unit depends on the magnetic susceptibility of the object being magnetized, in combination with its geometry/orientation. Magnetic susceptibility can thus be exploited as a source of tissue contrast, and susceptibility imaging may also become a useful tool in contrast agent quantification and for assessment of venous oxygen saturation levels. In this study, the accuracy of an established procedure for quantitative susceptibility mapping (QSM) was investigated. Three gel phantoms were constructed with cylinders of varying susceptibility and geometry. Experimental results were compared with simulated and analytically calculated data. An expected linear relationship between estimated susceptibility and concentration of contrast agent was observed. Less accurate QSM-based susceptibility values were observed for cylindrical objects at angles, relative to the main magnetic field, that were close to or larger than the magic angle. Results generally improved for large objects/high spatial resolution and large volume coverage. For simulated phase maps, accurate susceptibility quantification by QSM was achieved also for more challenging geometries. The investigated QSM algorithm was generally robust to changes in measurement and calculation parameters, but experimental phase data of sufficient quality may be difficult to obtain in certain geometries.
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| 20. |
- Scherman Rydhög, Anna, et al.
(författare)
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Intravoxel Incoherent Motion (IVIM) Imaging at Different Magnetic Field Strengths: What is Feasible?
- 2014
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Ingår i: Magnetic Resonance Imaging. - : Elsevier BV. - 1873-5894 .- 0730-725X. ; 32:10, s. 1247-1258
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Tidskriftsartikel (refereegranskat)abstract
- Due to limited SNR the cerebral applications of the intravoxel incoherent motion (IVIM) concept have been sparse. MRI hardware developments have resulted in improved SNR and this may justify a reassessment of IVIM imaging for non-invasive quantification of the cerebral blood volume (CBV) as a first step towards determining the optimal field strength.
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| 21. |
- Trinh, Lena, et al.
(författare)
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High-Resolution MR Imaging of Muscular Fat Fraction - Comparison of Three T2-Based Methods and Chemical Shift-Encoded Imaging
- 2017
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Ingår i: Tomography : a journal for imaging research. - : MDPI AG. - 2379-1381. ; 3:3, s. 153-162
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Tidskriftsartikel (refereegranskat)abstract
- Chemical shift-encoded imaging (CSEI) is the most common magnetic resonance imaging fat–water separation method. However, when high spatial resolution fat fraction (FF) images are desired, CSEI might be challenging owing to the increased interecho spacing. Here, 3 T2-based methods have been assessed as alternative methods for obtaining high-resolution FF images. Images from the calf of 10 healthy volunteers were acquired; FF maps were then estimated using 3 T2-based methods (2- and 3-parameter nonlinear least squares fit and a Bayesian probability method) and CSEI for reference. In addition, simulations were conducted to characterize the performance of various methods. Here, all T2-based methods resulted in qualitatively improved high-resolution FF images compared with high-resolution CSEI. The 2-parameter fit showed best quantitative agreement to low-resolution CSEI, even at low FF. The estimated T2-values of fat and water, and the estimated muscle FF of the calf, agreed well with previously published data. In conclusion, T2-based methods can provide improved high-resolution FF images of the calf compared with the CSEI method.
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| 22. |
- Wirestam, Ronnie, et al.
(författare)
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Dynamic susceptibility contrast perfusion MRI using phase-based venous output functions: : comparison with pseudo-continuous arterial spin labelling and assessment of contrast agent concentration in large veins.
- 2016
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Ingår i: Magnetic Resonance Materials in Physics, Biology, and Medicine. - : Springer Science and Business Media LLC. - 1352-8661 .- 0968-5243. ; 29:6, s. 823-831
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Contrast agent (CA) relaxivities are generally not well established in vivo, and the relationship between frequency/phase shift and magnetic susceptibility might be a useful alternative for CA quantification.MATERIALS AND METHODS: Twenty volunteers (25-84 years old) were investigated using test-retest pre-bolus dynamic susceptibility-contrast (DSC) magnetic resonance imaging (MRI). The pre-bolus phase-based venous output function (VOF) time integral was used for arterial input function (AIF) rescaling. Resulting cerebral blood flow (CBF) data for grey matter (GM) were compared with pseudo-continuous arterial spin labelling (ASL). During the main bolus CA passage, the apparent spatial shift (pixel shift) of the superior sagittal sinus (seen in single-shot echo-planar imaging (EPI)) was converted to CA concentration and compared with conventional ΔR2*-based data and with a predicted phase-based VOF from the pre-bolus experiment.RESULTS: The phase-based pre-bolus VOF resulted in a reasonable inter-individual GM CBF variability (coefficient of variation 28 %). Comparison with ASL CBF values implied a tissue R2*-relaxivity of 32 mM(-1) s(-1). Pixel-shift data at low concentrations (data not available at peak concentrations) were in reasonable agreement with the predicted phase-based VOF.CONCLUSION: Susceptibility-induced phase shifts and pixel shifts are potentially useful for large-vein CA quantification. Previous predictions of a higher R2*-relaxivity in tissue than in blood were supported.
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| 23. |
- Wirestam, Ronnie, et al.
(författare)
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Test-retest analysis of cerebral oxygen extraction estimates in healthy volunteers : comparison of methods based on quantitative susceptibility mapping and dynamic susceptibility contrast magnetic resonance imaging
- 2022
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Estimation of the oxygen extraction fraction (OEF) by quantitative susceptibility mapping (QSM) magnetic resonance imaging (MRI) is promising but requires systematic evaluation. Extraction of OEF-related information from the tissue residue function in dynamic susceptibility contrast MRI (DSC-MRI) has also been proposed. In this study, whole-brain OEF repeatability was investigated, as well as the relationships between QSM-based OEF and DSC-MRI-based parameters, i.e., mean transit time (MTT) and an oxygen extraction index, referred to as apparent OEF (AOEF). Method: Test-retest data were obtained from 20 healthy volunteers at 3 T. QSM maps were reconstructed from 3D gradient-echo MRI phase data, using morphology-enabled dipole inversion. DSC-MRI was accomplished using gradient-echo MRI at a temporal resolution of 1.24 s. Results: The whole-brain QSM-based OEF was (40.4±4.8) % and, in combination with a previously published cerebral blood flow (CBF) estimate, this corresponds to a cerebral metabolic rate of oxygen level of CMRO2 = 3.36 ml O2/min/100 g. The intra-class correlation coefficient [ICC(2,1)] for OEF test-retest data was 0.73. The MTT-versus-OEF and AOEF-versus-OEF relationships showed correlation coefficients of 0.61 (p = 0.004) and 0.52 (p = 0.019), respectively. Discussion: QSM-based OEF showed a convincing absolute level and good test-retest results in terms of the ICC. Moderate to good correlations between QSM-based OEF and DSC-MRI-based parameters were observed. The present results constitute an indicator of the level of robustness that can be achieved without applying extraordinary resources in terms of MRI equipment, imaging protocol, QSM reconstruction, and OEF analysis.
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