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Sökning: WFRF:(Kihlberg Johan 1970 )

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1.
  • Jackowski, Christian, 1975-, et al. (författare)
  • Quantitative MRI in Isotropic Spatial Resolution for Forensic Soft Tissue Documentation. Why and How?
  • 2011
  • Ingår i: Journal of Forensic Sciences. - : Blackwell. - 0022-1198 .- 1556-4029. ; 56:1, s. 208-215
  • Tidskriftsartikel (refereegranskat)abstract
    • A quantification of T1, T2, and PD in high isotropic resolution was performed on corpses. Isotropic and quantified postmortem magnetic resonance (IQpmMR) enables sophisticated 3D postprocessing, such as reformatting and volume rendering. The body tissues can be characterized by the combination of these three values. The values of T1, T2, and PD were given as coordinates in a T1-T2-PD space where similar tissue voxels formed clusters. Implementing in a volume rendering software enabled color encoding of specific tissues and pathologies in 3D models of the corpse similar to computed tomography, but with distinctively more powerful soft tissue discrimination. From IQpmMR data, any image plane at any contrast weighting may be calculated or 3D color-encoded volume rendering may be carried out. The introduced approach will enable future computer-aided diagnosis that, e.g., checks corpses for a hemorrhage distribution based on the knowledge of its T1-T2-PD vector behavior in a high spatial resolution.
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  • Bjällmark, Anna, et al. (författare)
  • Radiology departmental policy compliance with Swedish guidelines regarding post-contrast acute kidney injury for examinations with iodinated contrast media
  • 2021
  • Ingår i: Radiography. - : Elsevier. - 1078-8174 .- 1532-2831. ; 27:4, s. 1058-1063
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Guidelines concerning intravenous iodinated contrast media (CM) during computed tomography (CT) examinations are important to follow to minimize the risk for post-contrast acute kidney injury (PC-AKI). The purpose of this study was to investigate the radiology departmental policy compliance with Swedish guidelines concerning PC-AKI.METHODS: In February 2020, an electronic survey was distributed to the responsible radiographer at 41 radiology departments in all university hospitals and medium-sized hospitals in Sweden. The questions focused on routines around renal functional tests, individualized contrast administration and handling of patients with diabetes mellitus taking metformin.RESULTS: The response rate was 83%. Seventy-six percent (n = 26) of radiology departments calculated estimated glomerular filtration rate (eGFR) from serum creatinine prior to CM administration, but only 24% (n = 8) followed the recommendation to calculate eGFR from both serum creatinine and cystatin C. For acute/inpatients, 55% (n = 18) followed the recommendation that renal functional tests should be performed within 12 h before CM administration. For elective patients, 97% (n = 33) followed the recommendation to have eGFR newer than three months which is acceptable for patients with no history of disease that may have affected renal function. Approximately 80% of the radiology departments followed the recommendation that CM dose always should be individually adjusted to patient eGFR. Seventy-six percent (n = 26) followed the recommendation to continue with metformin at eGFR ≥ 45 ml/min.CONCLUSION: Compliance with the national guidelines was high regarding routines around renal functional tests, dose adjustment of CM and metformin discontinuation. Improvements can be made in using both cystatin C and serum creatinine for eGFR calculations as well as ensuring renal function tests within 12 h for acute/inpatients with acute disease that may affect renal function.IMPLICATIONS FOR PRACTICE: This study raises awareness of the importance of adhering to guidelines in healthcare. To have knowledge about the current level of compliance regarding PCI-AKI is important to maintain and develop effective clinical implementation of guidelines. The variation in practice seen in this study emphasizes the need of more effective implementation strategies to ensure adherence with best practice.
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  • Dahlqvist Leinhard, Olof, 1978-, et al. (författare)
  • Quantifying differences in hepatic uptake of the liver specific contrast agents Gd-EOB-DTPA and Gd-BOPTA : a pilot study
  • 2012
  • Ingår i: European Radiology. - : Springer Berlin/Heidelberg. - 0938-7994 .- 1432-1084. ; 22:3, s. 642-653
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives   To develop and evaluate a procedure for quantifying the hepatocyte-specific uptake of Gd-BOPTA and Gd-EOB-DTPA using dynamic contrast-enhanced (DCE) MRI. Methods   Ten healthy volunteers were prospectively recruited and 21 patients with suspected hepatobiliary disease were retrospectively evaluated. All subjects were examined with DCE-MRI using 0.025 mmol/kg of Gd-EOB-DTPA. The healthy volunteers underwent an additional examination using 0.05 mmol/kg of Gd-BOPTA. The signal intensities (SI) of liver and spleen parenchyma were obtained from unenhanced and enhanced acquisitions. Using pharmacokinetic models of the liver and spleen, and an SI rescaling procedure, a hepatic uptake rate, K Hep, estimate was derived. The K Hep values for Gd-EOB-DTPA were then studied in relation to those for Gd-BOPTA and to a clinical classification of the patient’s hepatobiliary dysfunction. Results   K Hep estimated using Gd-EOB-DTPA showed a significant Pearson correlation with K Hep estimated using Gd-BOPTA (r = 0.64; P < 0.05) in healthy subjects. Patients with impaired hepatobiliary function had significantly lower K Hep than patients with normal hepatobiliary function (K Hep = 0.09 ± 0.05 min-1 versus K Hep = 0.24 ± 0.10 min−1; P < 0.01). Conclusions   A new procedure for quantifying the hepatocyte-specific uptake of T 1-enhancing contrast agent was demonstrated and used to show that impaired hepatobiliary function severely influences the hepatic uptake of Gd-EOB-DTPA. Key Points   • The liver uptake of contrast agents may be measured with standard clinical MRI. • Calculation of liver contrast agent uptake is improved by considering splenic uptake. • Liver function affects the uptake of the liver-specific contrast agent Gd-EOB-DTPA. • Hepatic uptake of two contrast agents (Gd-EOB-DTPA, Gd-BOPTA) is correlated in healthy individuals. • This method can be useful for determining liver function, e.g. before hepatic surgery
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  • El-Saadi, Walid, 1984-, et al. (författare)
  • A head-to-head comparison of myocardial strain by fast-strain encoding and feature tracking imaging in acute myocardial infarction
  • 2022
  • Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media SA. - 2297-055X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundMyocardial infarction (MI) is a major cause of heart failure. Left ventricular adverse remodeling is common post-MI. Several studies have demonstrated a correlation between reduced myocardial strain and the development of adverse remodeling. Cardiac magnetic resonance (CMR) with fast-strain encoding (fast-SENC) or feature tracking (FT) enables rapid assessment of myocardial deformation. The aim of this study was to establish a head-to-head comparison of fast-SENC and FT in post-ST-elevated myocardial infarction (STEMI) patients, with clinical 2D speckle tracking echocardiography (2DEcho) as a reference. MethodsThirty patients treated with primary percutaneous coronary intervention for STEMI were investigated. All participants underwent CMR examination with late gadolinium enhancement, cine-loop steady-state free precession, and fast-SENC imaging using a 1.5T scanner as well as a 2DEcho. Global longitudinal strain (GLS), segmental longitudinal strain (SLS), global circumferential strain (GCS), and segmental circumferential strain (SCS) were assessed along with the MI scar extent. ResultsThe GCS measurements from fast-SENC and FT were nearly identical: the mean difference was 0.01 (2.5)% (95% CI - 0.92 to 0.95). For GLS, fast-SENC values were higher than FT, with a mean difference of 1.8 (1.4)% (95% CI 1.31-2.35). Tests of significance for GLS did not show any differences between the MR methods and 2DEcho. Average strain in the infarct-related artery (IRA) segments compared to the remote myocardium was significantly lower for the left anterior descending artery and right coronary artery culprits but not for the left circumflex artery culprits. Fast-SENC displayed a higher area under the curve for detecting infarcted segments than FT for both SCS and SLS. ConclusionGLS and GCS did not significantly differ between fast-SENC and FT. Both showed acceptable agreement with 2DEcho for longitudinal strain. Segments perfused by the IRA showed significantly reduced strain values compared to the remote myocardium. Fast-SENC presented a higher sensitivity and specificity for detecting infarcted segments than FT.
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  • Forsgren, Mikael, et al. (författare)
  • Comparing 2D and 3D Magnetic Resonance Elastography Techniques in a Clinical Setting: Initial Experiences
  • 2014
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Purpose: It has been shown that liver fibrosis, and even cirrhosis, may be reversible in humans. For this reason there is a great need for the imminent introduction of non-invasive and clinically useful methods in order to monitor fibrosis in patients [1, 2]. A body of evidence points to the fact that MRE is a highly useful candidate towards this end [3]. However, before using such techniques more widely, it is important to verify that comparable physical measures are provided by alternative and clinically relevant MRE approaches. The aim of this pilot study was to compare 2D and 3D MRE, also known as MR Rheology, using a commercially available 2D system, with an acoustic transducer, and 3D MRE research system, with an electromagnetic transducer, with respect to liver stiffness and elasticity in patients with diffuse or suspected diffuse liver disease. Materials and Methods: Seven patients, referred to our hospital for evaluation of elevated serum alanine aminotransferase (ALT) and/or alkaline phosphatase (ALP) levels but without signs of cirrhosis on physical examination, were recruited from a previous study [4], and examined in the course of one day. Fibrosis staging from prior biopsy were gained from [4], see Table 1. The 3D MRE method included an active electromagnetic transducer generating waves at 56 Hz, and a 1.5 T Philips Achieva MR-scanner, with a phased array body coil (Sense TorsoXL, all 16 coil elements), GRE sequence parameters include; FOV = 320x256 mm2, matrix = 80x38, slice thickness = 4 mm, # slices = 9, FA = 15°, TR = 112 ms, TE = 9.21 ms, SENSE = 2. The 2D MRE method included a passive acoustic transducer generating waves at 60 Hz, and a 1.5 T GE 450W MR-scanner, with a phased array body coil (HD8 Torso, all 8 coil elements), GRE sequence parameters include; FOV = 440x440 mm2, matrix = 256x64, slice thickness = 10 mm, # slices = 4, FA = 30°, TR = 50 ms, TE = 21.7 ms, ASSET = 2. The transducers were on both systems placed on the anterior chest wall to the right of xiphoid process (patient in a supine position), the time between each MRE acquisition was dependent on how long it took to transfer the patient between the two MR systems in the hospital (<10 min) A region of interest (ROI) was placed in an appropriate single 10 mm slice acquired using the GE MR-scanner. A corresponding ROI for the Philips system, covering the same anatomical region, was placed over three slices (4 mm thickness each). This yielded a total cranio-caudal coverage of the ROIs equal to 10 mm (on the GE data) and 12 mm (on the Philips data). The mean and standard deviations of the stiffness (GE), elasticity (Philips) and Gabs,Elastic (Philips) were calculated. Gabs,Elastic is the absolute value of the shear modulus, which in principle is equivalent to the viscoelastic property, shear stiffness. In the 3D method the shear waves were obtained by applying the curl operator and using the Voigt rheological model to obtain shear elasticity maps [5, 6]. In the 2D method the GE system provided the stiffness maps. Statistics was performed using Mathematica 9. ROI drawing and quantification of the data from the GE system was performed using Sectra PACS IDS7, and ROI drawing and quantification of the data from the Philips system was performed using a custom software package implemented in ROOT, generously provided by R. Sinkus (Kings College, London, UK). Results: The measured values are presented in Table 1. Both elasticity and Gabs,Elastic correlates well with the stiffness measurement carried out in the GE system (Fig. 1), as was shown by the elasticity and stiffness correlation R2 = 0.96 (P < 0.001) slope = 1.08 (P < 0.001), intercept = 0.61 kPa (P = 0.08), Gabs,Elastic and stiffness correlation R2 = 0.96 (P < 0.001), slope = 0.95 (P< 0.001) intercept = 0.28 kPa (P = 0.43)
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  • Forsgren, Mikael, et al. (författare)
  • Comparing hepatic 2D and 3D magnetic resonance elastography methods in a clinical setting – Initial experiences
  • 2015
  • Ingår i: European Journal of Radiology Open. - : Elsevier. - 2352-0477. ; 2, s. 66-70
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposeContinuous monitoring of liver fibrosis progression in patients is not feasible with the current diagnostic golden standard (needle biopsy). Recently, magnetic resonance elastography (MRE) has emerged as a promising method for such continuous monitoring. Since there are different MRE methods that could be used in a clinical setting there is a need to investigate whether measurements produced by these MRE methods are comparable. Hence, the purpose of this pilot study was to evaluate whether the measurements of the viscoelastic properties produced by 2D (stiffness) and 3D (elasticity and ‘Gabs,Elastic’) MRE are comparable.Materials and methodsSeven patients with diffuse or suspect diffuse liver disease were examined in the same day with the two MRE methods. 2D MRE was performed using an acoustic passive transducer, with a 1.5 T GE 450 W MR system. 3D MRE was performed using an electromagnetic active transducer, with a 1.5 T Philips Achieva MR system. Finally, mean viscoelastic values were extracted from the same anatomical region for both methods by an experienced radiologist.ResultsStiffness correlated well with the elasticity, R2 = 0.96 (P < 0.001; slope = 1.08, intercept = 0.61 kPa), as well as with ‘Gabs,Elastic’ R2 = 0.96 (P < 0.001; slope = 0.95, intercept = 0.28 kPa).ConclusionThis pilot study shows that different MRE methods can produce comparable measurements of the viscoelastic properties of the liver. The existence of such comparable measurements is important, both from a clinical as well as a research perspective, since it allows for equipment-independent monitoring of disease progression.
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  • Kihlberg, Johan, 1970-, et al. (författare)
  • Ackumulering av överskottsjärn kan bestämmas med MR
  • 2009
  • Ingår i: Ackumulering av överskottsjärn kan bestämmas med MR.
  • Konferensbidrag (refereegranskat)abstract
    • Järnöverskott kan vara toxiskt i kroppen. Järnöverskott ses fr a efter multipla blodtransfusioner vid vissa blodsjukdomar. Internationellt är den vanligaste orsaken thalassemi. Antalet patienter med denna problematik är i Sverige ännu begränsat. Järnöverskott kan leda till allvarlig, svårbehandlad hjärtsvikt man kan behandlas med chelaterande perorala läkemedel och styrs då i allmänhet utifrån ferritin/s. Vår hypotes var att överensstämmelsen mellan järnöverskott och transferrin är låg, att järnöverskott bättre karaktäriseras med MR som också kan differentiera mellan järnöverskott i  hjärta respektive lever.
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  • Kihlberg, Johan, 1970-, et al. (författare)
  • Clinical experience of strain imaging using DENSE for detecting infarcted cardiac segments
  • 2015
  • Ingår i: Journal of Cardiovascular Magnetic Resonance. - : BioMed Central. - 1097-6647 .- 1532-429X. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundWe hypothesised that myocardial deformation determined with magnetic resonance imaging (MRI) will detect myocardial scar.MethodsDisplacement Encoding with Stimulated Echoes (DENSE) was used to calculate left ventricular strain in 125 patients (29 women and 96 men) with suspected coronary artery disease. The patients also underwent cine imaging and late gadolinium enhancement. 57 patients had a scar area >1 % in at least one segment, 23 were considered free from coronary artery disease (control group) and 45 had pathological findings but no scar (mixed group). Peak strain was calculated in eight combinations: radial and circumferential strain in transmural, subendocardial and epicardial layers derived from short axis acquisition, and transmural longitudinal and radial strain derived from long axis acquisitions. In addition, the difference between strain in affected segments and reference segments, “differential strain”, from the control group was analysed.ResultsIn receiver-operator-characteristic analysis for the detection of 50 % transmurality, circumferential strain performed best with area-under-curve (AUC) of 0.94. Using a cut-off value of -17 %, sensitivity was 95 % at a specificity of 80 %. AUC did not further improve with differential strain. There were significant differences between the control group and global strain circumferential direction (-17 % versus -12 %) and in the longitudinal direction (-13 % versus -10 %). Interobserver and scan-rescan reproducibility was high with an intraclass correlation coefficient (ICC) >0.93.ConclusionsDENSE-derived circumferential strain may be used for the detection of myocardial segments with >50 % scar area. The repeatability of strain is satisfactory. DENSE-derived global strain agrees with other global measures of left ventricular ejection fraction.
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  • Kihlberg, Johan, Medicine doktor, 1970-, et al. (författare)
  • Clinical validation of three cardiovascular magnetic resonance techniques to measure strain and torsion in patients with suspected coronary artery disease
  • 2020
  • Ingår i: Journal of Cardiovascular Magnetic Resonance. - : BioMed Central. - 1097-6647 .- 1532-429X. ; 22:83
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundSeveral cardiovascular magnetic resonance (CMR) techniques can measure myocardial strain and torsion with high accuracy. The purpose of this study was to compare displacement encoding with stimulated echoes (DENSE), tagging and feature tracking (FT) for measuring circumferential and radial myocardial strain and myocardial torsion in order to assess myocardial function and infarct scar burden both at a global and at a segmental level.Method116 patients with a high likelihood of coronary artery disease (European SCORE > 15%) underwent CMR examination including cine images, tagging, DENSE and late gadolinium enhancement (LGE) in the short axis direction. In total, 97 patients had signs of myocardial disease and 19 had no abnormalities in terms of left ventricular (LV) wall mass index, LV ejection fraction, wall motion, LGE or a history of myocardial infarction. Thirty-four patients had myocardial infarct scar with a transmural LGE extent (transmurality) that exceeded 50% of the wall thickness in at least one segment. Global circumferential strain (GCS) and global radial strain (GRS) was analyzed using FT of cine loops, deformation of tag lines or DENSE displacement.ResultsDENSE and tagging both showed high sensitivity (82% and 71%) at a specificity of 80% for the detection of segments with > 50% LGE transmurality, and receiver operating characteristics (ROC) analysis showed significantly higher area under the curve-values (AUC) for DENSE (0.87) than for tagging (0.83, p < 0.001) and FT (0.66, p = 0.003). GCS correlated with global LGE when determined with DENSE (r = 0.41), tagging (r = 0.37) and FT (r = 0.15). GRS had a low but significant negative correlation with LGE; DENSE r = − 0.10, FT r = − 0.07 and tagging r = − 0.16. Torsion from DENSE and tagging had a weak correlation (− 0.20 and − 0.22 respectively) with global LGE.ConclusionCircumferential strain from DENSE detected segments with > 50% scar with a higher AUC than strain determined from tagging and FT at a segmental level. GCS and torsion computed from DENSE and tagging showed similar correlation with global scar size, while when computed from FT, the correlation was lower.
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  • Kihlberg, Johan, Medicine doktor, 1970-, et al. (författare)
  • Magnetic resonance imaging incidents are severely underreported : a finding in a multicentre interview survey
  • 2022
  • Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 32:1, s. 477-488
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The purpose of this study was to develop a procedure to investigate the occurrence, character and causes of magnetic resonance (MR) imaging incidents. Methods: A semi-structured questionnaire was developed containing details such as safety zones, examination complexity, staff MR knowledge, staff categories, and implementation of EU directive 2013/35. We focused on formally reported incidents that had occurred during 2014–2019, and unreported incidents during one year. Thirteen clinical MR units were visited, and the managing radiographer was interviewed. Open questions were analysed using conventionally adopted content analysis. Results: Thirty-seven written reports for 5 years and an additional 12 oral reports for 1 year were analysed. Only 38% of the incidents were reported formally. Some of these incidents were catastrophic. Negative correlations were observed between the number of annual incidents (per scanner) and staff MR knowledge (Spearman’s rho − 0.41, p < 0.05) as well as the number of MR physicists per scanner (− 0.48, p < 0.05). It was notable that only half of the sites had implemented the EU directive. Quotes like ‘Burns are to be expected in MR’ and not even knowing the name of the incident reporting system suggested an inadequate safety culture. Finally, there was a desire among staff for MR safety education. Conclusions: MR-related incidents were greatly underreported, and some incidents could have had catastrophic outcomes. There is a great desire among radiographers to enhance the safety culture, but to achieve this, much more accessible education is required, as well as focused involvement of the management of the operations. Key Points: • Only one in three magnetic resonance–related incidents were reported. • Several magnetic resonance incidents could have led to catastrophic consequences. • Much increased knowledge about magnetic resonance safety is needed by radiologists and radiographers.
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  • Kihlberg, Johan, 1970- (författare)
  • Magnetic Resonance Imaging of Myocardial Deformation and Scarring in Coronary Artery Disease.
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Although improved treatments have reduced the rates of acute complications from myocardial infarction, sequelae such as heart failure and sudden death threaten the future wellbeing of those patients. Secondary prevention after myocardial infarction is related to cardiovascular risk factors and the effect of the infarct on left ventricular function. Cardiovascular magnetic resonance imaging (CMR) is necessary to determine the size of the infarct scar and can with great precision determine left ventricular volumes, left ventricular ejection fraction, and deformation (strain and torsion). The purpose of this thesis was to improve on CMR methods to facilitate image acquisition and post processing in patients with high risk of coronary artery disease (CAD).In Paper 1, a three-dimensional phase-sensitive inversion-recovery (3D PSIR) sequence was modified to measure T1 during a single breath hold. The measured T1 values were used to extrapolate a map of T1 relaxation, which avoided the time-consuming manual determination of the inversion time. The data collection consisted of phantom experiments, Monte Carlo simulations of the effect of various heart rates, and clinical investigation of 18 patients with myocardial infarction. Scar images created with the modified sequence were compared to those created with the standard sequence. The 3D PSIR sequence was able to measure T1 relaxation with a high accuracy up to 800 ms, which is in the suitable range for scar imaging. Simulated arrhythmias showed that the method was robust and able to tolerate some variation in heart rate. The modified sequence provides measurements of inversion time that can be used to facilitate standard scar imaging or to reconstruct synthetic scar images. Images of infarct scar obtained with the 3D PSIR sequence bore striking similarity to images obtained with the standard sequence.In Paper 2, 125 patients with high risk of CAD were investigated using the displacement encoding with stimulated echoes (DENSE) sequence. Image segments with infarct scar area >50% (transmurality) could be identified with a sensitivity of 95% and a specificity of 80% based on circumferential strain calculated from the DENSE measurements. The DENSE sequence was also applied in other directions, but its sensitivity and specificity to detect scar was lower than when used for circumferential strain.In Paper 3, 90 patients with high risk of CAD were examined by DENSE, tagging with harmonic phase (HARP) imaging and cine imaging with feature tracking (FT), to detect cardiac abnormalities as manifested in end-systolic circumferential strain. Circumferential strain calculated with DENSE had higher sensitivity and specificity than the competing methods to detect infarction with transmurality >50%. Global circumferential strain measured by DENSE correlated better with global parameters such as left ventricular ejection fraction, myocardial wall mass, left ventricular end-diastolic and end-systolic volume; than strain measured by FT or HARP.In Paper 4, myocardial torsion was investigated using DENSE, HARP, and FT in 48 patients with high risk of CAD. Torsion measured by each of the three methods was correlated with other global measures such as left ventricular ejection fraction, left ventricular mass, and left ventricular end-diastolic and end-systolic volumes. The torsion measurements obtained with DENSE had a stronger relationship with left ventricular ejection fraction, left ventricular mass, and volumes than those obtained with HARP or FT.DENSE was superior to the other methods for strain and torsion measurement and can be used to describe myocardial deformation quantitatively and objectively.
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  • Lindgren, Cecilia, et al. (författare)
  • Dynamics Determine Signaling in a Multicomponent System Associated with Rheumatoid Arthritis
  • 2018
  • Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 61:11, s. 4774-4790
  • Tidskriftsartikel (refereegranskat)abstract
    • Strategies that target multiple components are usually required for treatment of diseases originating from complex biological systems. The multicomponent system consisting of the DR4 major histocompatibility complex type II molecule, the glycopeptide CI1259-273 from type II collagen, and a T-cell receptor is associated with development of rheumatoid arthritis (RA). We introduced non-native amino acids and amide bond isosteres into CI1259-273 and investigated the effect on binding to DR4 and the subsequent T-cell response. Molecular dynamics simulations revealed that complexes between DR4 and derivatives of CI1259-273 were highly dynamic. Signaling in the overall multicomponent system was found to depend on formation of an appropriate number of dynamic intramolecular hydrogen bonds between DR4 and CI1259-273, together with the positioning of the galactose moiety of CI1259-273 in the DR4 binding groove. Interestingly, the system tolerated modifications at several positions in CI1259-273, indicating opportunities to use analogues to increase our understanding of how rheumatoid arthritis develops and for evaluation as vaccines to treat RA.
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  • Lundberg, Peter, 1958-, et al. (författare)
  • Breast density is strongly associated with multiparametric magnetic resonance imaging biomarkers and pro-tumorigenic proteins in situ
  • 2022
  • Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 127, s. 2025-2033
  • Tidskriftsartikel (refereegranskat)abstract
    • Background High mammographic density is an independent risk factor for breast cancer by poorly understood molecular mechanisms. Women with dense breasts often undergo conventional magnetic resonance imaging (MRI) despite its limited specificity, which may be increased by diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) and contrast. How these modalities are affected by breast density per se and their association with the local microenvironment are undetermined. Methods Healthy postmenopausal women attending mammography screen with extremely dense or entirely fatty breasts underwent multiparametric MRI for analyses of lean tissue fraction (LTF), ADC and perfusion dynamics. Microdialysis was used for extracellular proteomics in situ. Results Significantly increased LTF and ADC and delayed perfusion were detected in dense breasts. In total, 270 proteins were quantified, whereof 124 related to inflammation, angiogenesis, and cellular growth were significantly upregulated in dense breasts. Most of these correlated significantly with LTF, ADC and the perfusion data. Conclusions ADC and perfusion characteristics depend on breast density, which should be considered during the implementation of thresholds for malignant lesions. Dense and nondense breasts are two essentially different biological entities, with a pro-tumorigenic microenvironment in dense breasts. Our data reveal several novel pathways that may be explored for breast cancer prevention strategies.
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  • Norén, Bengt, et al. (författare)
  • Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA
  • 2013
  • Ingår i: European Radiology. - : Springer. - 0938-7994 .- 1432-1084. ; 23:1, s. 174-181
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesTo apply dynamic contrast-enhanced (DCE) MRI on patients presenting with elevated liver enzymes without clinical signs of hepatic decompensation in order to quantitatively compare the hepatocyte-specific uptake of Gd-EOB-DTPA with histopathological fibrosis stage.MethodsA total of 38 patients were prospectively examined using 1.5-T MRI. Data were acquired from regions of interest in the liver and spleen by using time series of single-breath-hold symmetrically sampled two-point Dixon 3D images (non-enhanced, arterial and venous portal phase; 3, 10, 20 and 30 min) following a bolus injection of Gd-EOB-DTPA (0.025 mmol/kg). The signal intensity (SI) values were reconstructed using a phase-sensitive technique and normalised using multiscale adaptive normalising averaging (MANA). Liver-to-spleen contrast ratios (LSC_N) and the contrast uptake rate (KHep) were calculated. Liver biopsy was performed and classified according to the Batts and Ludwig system.ResultsArea under the receiver-operating characteristic curve (AUROC) values of 0.71, 0.80 and 0.78, respectively, were found for KHep, LSC_N10 and LSC_N20 with regard to severe versus mild fibrosis. Significant group differences were found for KHep (borderline), LSC_N10 and LSC_N20.ConclusionsLiver fibrosis stage strongly influences the hepatocyte-specific uptake of Gd-EOB-DTPA. Potentially the normalisation technique and KHep will reduce patient and system bias, yielding a robust approach to non-invasive liver function determination.
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