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Sökning: WFRF:(Neubauer Stefan)

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1.
  • Ricci, Fabrizio, et al. (författare)
  • Cardiovascular magnetic resonance reference values of mitral and tricuspid annular dimensions : the UK Biobank cohort
  • 2021
  • Ingår i: Journal of Cardiovascular Magnetic Resonance. - : Springer Science and Business Media LLC. - 1097-6647 .- 1532-429X. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mitral valve (MV) and tricuspid valve (TV) apparatus geometry are essential to define mechanisms and etiologies of regurgitation and to inform surgical or transcatheter interventions. Given the increasing use of cardiovascular magnetic resonance (CMR) for the evaluation of valvular heart disease, we aimed to establish CMR-derived age- and sex-specific reference values for mitral annular (MA) and tricuspid annular (TA) dimensions and tethering indices derived from truly healthy Caucasian adults. Methods: 5065 consecutive UK Biobank participants underwent CMR using cine balanced steady-state free precession imaging at 1.5 T. Participants with non-Caucasian ethnicity, prevalent cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Absolute and indexed reference ranges for MA and TA diameters and tethering indices were stratified by gender and age (45–54, 55–64, 65–74 years). Results: Overall, 721 (14.2%) truly healthy participants aged 45–74 years (54% women) formed the reference cohort. Absolute MA and TA diameters, MV tenting length and MV tenting area, were significantly larger in men. Mean ± standard deviation (SD) end-diastolic and end-systolic MA diameters in the 3-chamber view (anteroposterior diameter) were 2.9 ± 0.4 cm (1.5 ± 0.2 cm/m2) and 3.3 ± 0.4 cm (1.7 ± 0.2 cm/m2) in men, and 2.6 ± 0.4 cm (1.6 ± 0.2 cm/m2) and 3.0 ± 0.4 cm (1.8 ± 0.2 cm/m2) in women, respectively. Mean ± SD end-diastolic and end-systolic TA diameters in the 4-chamber view were 3.2 ± 0.5 cm (1.6 ± 0.3 cm/m2) and 3.2 ± 0.5 cm (1.7 ± 0.3 cm/m2) in men, and 2.9 ± 0.4 cm (1.7 ± 0.2 cm/m2) and 2.8 ± 0.4 cm (1.7 ± 0.3 cm/m2) in women, respectively. With advancing age, end-diastolic TA diameter became larger and posterior MV leaflet angle smaller in both sexes. Reproducibility of measurements was good to excellent with an inter-rater intraclass correlation coefficient (ICC) between 0.92 and 0.98 and an intra-rater ICC between 0.90 and 0.97. Conclusions: We described age- and sex-specific reference ranges of MA and TA dimensions and tethering indices in the largest validated healthy Caucasian population. Reference ranges presented in this study may help to improve the distinction between normal and pathological states, prompting the identification of subjects that may benefit from advanced cardiac imaging for annular sizing and planning of valvular interventions.
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2.
  • Ashkir, Zakariye, et al. (författare)
  • Four-dimensional flow cardiac magnetic resonance assessment of left ventricular diastolic function
  • 2022
  • Ingår i: Frontiers in Cardiovascular Medicine. - : FRONTIERS MEDIA SA. - 2297-055X. ; 9
  • Forskningsöversikt (refereegranskat)abstract
    • Left ventricular diastolic dysfunction is a major cause of heart failure and carries a poor prognosis. Assessment of left ventricular diastolic function however remains challenging for both echocardiography and conventional phase contrast cardiac magnetic resonance. Amongst other limitations, both are restricted to measuring velocity in a single direction or plane, thereby compromising their ability to capture complex diastolic hemodynamics in health and disease. Time-resolved three-dimensional phase contrast cardiac magnetic resonance imaging with three-directional velocity encoding known as 4D flow CMR is an emerging technology which allows retrospective measurement of velocity and by extension flow at any point in the acquired 3D data volume. With 4D flow CMR, complex aspects of blood flow and ventricular function can be studied throughout the cardiac cycle. 4D flow CMR can facilitate the visualization of functional blood flow components and flow vortices as well as the quantification of novel hemodynamic and functional parameters such as kinetic energy, relative pressure, energy loss and vorticity. In this review, we examine key concepts and novel markers of diastolic function obtained by flow pattern analysis using 4D flow CMR. We consolidate the existing evidence base to highlight the strengths and limitations of 4D flow CMR techniques in the surveillance and diagnosis of left ventricular diastolic dysfunction.
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3.
  • Cronholm, Stefan, et al. (författare)
  • Guiding situated method transfer in design and evaluation
  • 2013
  • Ingår i: Universal Access in the Information Society. - : Springer. - 1615-5289 .- 1615-5297. ; 14:2, s. 151-168
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose is to suggest guidelines for supporting the transfer of design and evaluation methods from one organization/field/sector to another. There exist a variety of methods for designing and evaluating interactive socio-technical systems. Many of them have been developed for dedicated purposes, such as heuristic evaluation, referring to specific situations and artifacts. Due to the recent diversification of devices and the continuing diffusion of society with interactive systems, applying design and evaluation methods in an effective and efficient way has become crucial, in particular when operating under tight economic conditions and demanding user constraints. Learning from other projects, cases, disciplines or sectors seems to be one way to effectively apply methods in design and evaluation. In order to validate the suggested guidelines, the guidelines are theoretically informed and empirically supported by the use of a case study. The results consist of a set of seven guidelines for method transfer. The guidelines are described in terms of questions to ask, expected input and expected output and how they relate to the other guidelines. Transferring methods require an informed procedure, reflecting the rationale of methods, application-specific factors and experience of use. In this paper, some conceptual foundations are given when exploring transferability of methods and implemented in the field of IT cross-sector developments. The developed guidelines allow developers to identify situation-specific elements and design an effective learning experience for a case at hand. The introduced content structure and interactive features show an effective way of developer support.
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4.
  • Dyverfeldt, Petter, et al. (författare)
  • 4D flow cardiovascular magnetic resonance consensus statement
  • 2015
  • Ingår i: Journal of Cardiovascular Magnetic Resonance. - : BioMed Central / Informa Healthcare. - 1097-6647 .- 1532-429X. ; 17:72
  • Forskningsöversikt (refereegranskat)abstract
    • Pulsatile blood flow through the cavities of the heart and great vessels is time-varying and multidirectional. Access to all regions, phases and directions of cardiovascular flows has formerly been limited. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has enabled more comprehensive access to such flows, with typical spatial resolution of 1.5x1.5x1.5 - 3x3x3 mm(3), typical temporal resolution of 30-40 ms, and acquisition times in the order of 5 to 25 min. This consensus paper is the work of physicists, physicians and biomedical engineers, active in the development and implementation of 4D Flow CMR, who have repeatedly met to share experience and ideas. The paper aims to assist understanding of acquisition and analysis methods, and their potential clinical applications with a focus on the heart and greater vessels. We describe that 4D Flow CMR can be clinically advantageous because placement of a single acquisition volume is straightforward and enables flow through any plane across it to be calculated retrospectively and with good accuracy. We also specify research and development goals that have yet to be satisfactorily achieved. Derived flow parameters, generally needing further development or validation for clinical use, include measurements of wall shear stress, pressure difference, turbulent kinetic energy, and intracardiac flow components. The dependence of measurement accuracy on acquisition parameters is considered, as are the uses of different visualization strategies for appropriate representation of time-varying multidirectional flow fields. Finally, we offer suggestions for more consistent, user-friendly implementation of 4D Flow CMR acquisition and data handling with a view to multicenter studies and more widespread adoption of the approach in routine clinical investigations.
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5.
  • Paetzold, Martin, et al. (författare)
  • Rosetta Radio Science Investigations (RSI)
  • 2007
  • Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 128:1-4, s. 599-627
  • Forskningsöversikt (refereegranskat)abstract
    • The Rosetta spacecraft has been successfully launched on 2nd March 2004 to its new target comet 67 P/Churyurnov-Gerasimenko. The science objectives of the Rosetta Radio Science Investigations (RSI) experiment address fundamental aspects of cometary physics such as the mass and bulk density of the nucleus, its gravity field, its interplanetary orbit perturbed by nongravitational forces, its size and shape, its internal structure, the composition and roughness of the nucleus surface, the abundance of large dust grains, the plasma content in the coma and the combined dust and gas mass flux. The masses of two asteroids, Steins and Lutetia, shall be determined during flybys in 2008 and 2010. respectively. Secondary objectives are the radio sounding of the solar corona during the superior conjunctions of the spacecraft with the Sun during the cruise phase. The radio carrier links of the spacecraft Telemetry, Tracking and Command (TT&C) subsystem between the orbiter and the Earth will be used for these investigations. An Ultrastable oscillator (USO) connected to both transponders of the radio subsystem serves as a stable frequency reference source for both radio downlinks at X-band (8.4 GHz) and S-band (2.3 GHz) in the one-way mode. The Simultaneous and coherent dual-frequency downlinks via the High Gain Antenna (HGA) permit separation of contributions from the classical Doppler shift and the dispersive media effects caused by the motion of the spacecraft with respect to the Earth and the propagation of the signals through the dispersive media, respectively.
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6.
  • Parisinos, Constantinos A., et al. (författare)
  • Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis
  • 2020
  • Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 73:2, s. 241-251
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundA non-invasive method to grade the severity of steatohepatitis and liver fibrosis is magnetic resonance imaging (MRI) based corrected T1 (cT1). We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases.MethodsFirst, we performed a genome-wide association study (GWAS) in 14,440 Europeans in UK Biobank with liver cT1 measures. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures.ResultsWe identified six independent genetic variants associated with liver cT1 that reached GWAS significance threshold (p<5x10-8). Four of the variants (rs75935921 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated transaminases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and BMI were causally associated with elevated cT1 whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective.ConclusionThe association between two metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at risk individuals.
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7.
  • Pavlides, Michael, et al. (författare)
  • Liver investigation: Testing marker utility in steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol
  • 2023
  • Ingår i: Contemporary Clinical Trials. - : ELSEVIER SCIENCE INC. - 1551-7144 .- 1559-2030. ; 134
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721
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8.
  • Petersen, Steffen E, et al. (författare)
  • Differentiation of athlete's heart from pathological forms of cardiac hypertrophy by means of geometric indices derived from cardiovascular magnetic resonance.
  • 2005
  • Ingår i: Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance. - 1097-6647. ; 7:3, s. 551-8
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Determination of the underlying etiology of left ventricular hypertrophy (LVH) is a common, challenging, and critical clinical problem. The authors aimed to test whether pathological LVH, such as occurs in hypertrophic cardiomyopathy (HCM), hypertensive heart disease, or aortic stenosis, and physiological LVH in athletes, can be distinguished by means of left ventricular volume and geometric indices, derived from cardiovascular magnetic resonance imaging. METHODS: A total of 120 subjects were studied on a 1.5 Tesla MR (Sonata, Siemens Medical Solutions, Erlangen, Germany) scanner, comprising healthy volunteers (18), competitive athletes (25), patients with HCM (35), aortic stenosis (24), and hypertensive heart disease (18). Left ventricular mass index, ejection fraction, end-diastolic, end-systolic and stroke volume index, diastolic wall thickness, wall thickness ratio and diastolic and systolic wall-to-volume ratios were determined. RESULTS: Left ventricular (LV) mass indices were similar for all forms of LVH (p > 0.05), which were at least 35% higher than those obtained in healthy volunteers (p < 0.05). Multiple logistic regression showed that the percentage of correctly predicted diagnoses was 100% for athlete's heart, 80% for hypertrophic cardiomyopathy, 54% for aortic stenosis, and 22% for hypertensive heart disease. Using a receiver operating curve-determined cut-off value for diastolic wall-to-volume ratio of less than 0.15 mm x m2 x ml(-1), athletes' hearts could be differentiated from all forms of pathological cardiac hypertrophy with 99% specificity. CONCLUSIONS: Athlete's heart can be reliably distinguished from all forms of pathological cardiac hypertrophy using CMR-derived LV volume and geometric indices, but pathological forms of LVH present with overlapping cardiac hypertrophy phenotypes. This capability of CMR should be of high clinical value.
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9.
  • Redmer, Torben, et al. (författare)
  • JUN mediates the senescence associated secretory phenotype and immune cell recruitment to prevent prostate cancer progression
  • 2024
  • Ingår i: Molecular Cancer. - : BioMed Central (BMC). - 1476-4598. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Prostate cancer develops through malignant transformation of the prostate epithelium in a stepwise, mutation-driven process. Although activator protein-1 transcription factors such as JUN have been implicated as potential oncogenic drivers, the molecular programs contributing to prostate cancer progression are not fully understood.Methods: We analyzed JUN expression in clinical prostate cancer samples across different stages and investigated its functional role in a Pten-deficient mouse model. We performed histopathological examinations, transcriptomic analyses and explored the senescence-associated secretory phenotype in the tumor microenvironment.Results: Elevated JUN levels characterized early-stage prostate cancer and predicted improved survival in human and murine samples. Immune-phenotyping of Pten-deficient prostates revealed high accumulation of tumor-infiltrating leukocytes, particularly innate immune cells, neutrophils and macrophages as well as high levels of STAT3 activation and IL-1β production. Jun depletion in a Pten-deficient background prevented immune cell attraction which was accompanied by significant reduction of active STAT3 and IL-1β and accelerated prostate tumor growth. Comparative transcriptome profiling of prostate epithelial cells revealed a senescence-associated gene signature, upregulation of pro-inflammatory processes involved in immune cell attraction and of chemokines such as IL-1β, TNF-α, CCL3 and CCL8 in Pten-deficient prostates. Strikingly, JUN depletion reversed both the senescence-associated secretory phenotype and senescence-associated immune cell infiltration but had no impact on cell cycle arrest. As a result, JUN depletion in Pten-deficient prostates interfered with the senescence-associated immune clearance and accelerated tumor growth.Conclusions: Our results suggest that JUN acts as tumor-suppressor and decelerates the progression of prostate cancer by transcriptional regulation of senescence- and inflammation-associated genes. This study opens avenues for novel treatment strategies that could impede disease progression and improve patient outcomes. Graphical Abstract: (Figure presented.).
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10.
  • Salerno, Michael, et al. (författare)
  • Recent Advances in Cardiovascular Magnetic Resonance
  • 2017
  • Ingår i: Circulation: Cardiovascular Imaging. - 1941-9651. ; 10:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiovascular magnetic resonance imaging has become the gold standard for evaluating myocardial function, volumes, and scarring. Additionally, cardiovascular magnetic resonance imaging is unique in its comprehensive tissue characterization, including assessment of myocardial edema, myocardial siderosis, myocardial perfusion, and diffuse myocardial fibrosis. Cardiovascular magnetic resonance imaging has become an indispensable tool in the evaluation of congenital heart disease, heart failure, cardiac masses, pericardial disease, and coronary artery disease. This review will highlight some recent novel cardiovascular magnetic resonance imaging techniques, concepts, and applications.
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