Search

Background The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance. Methods and findings A phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40-69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabolic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, coronary atherosclerosis, ischemic heart disease, chronic ischemic heart disease, myocardial infarction, and hypercholesterolemia) that were associated with genetically determined serum urate levels after multiple testing correction (p < 3.35 x 10.sup.-4). TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases, and blood lipid levels but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with CVDs. The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and possible misclassification of cases for mild disease that did not require hospitalization. Conclusion In this study, high serum urate levels were found to be associated with increased risk of different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a common mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities., Author(s): Xue Li 1, Xiangrui Meng 1, Yazhou He 1, Athina Spiliopoulou 2, Maria Timofeeva 3, Wei-Qi Wei 4, Aliya Gifford 4, Tian Yang 1, Tim Varley 5, Ioanna Tzoulaki [...]

Objectives: We aimed to investigate the role of serum uric acid (SUA) level in a broad spectrum of disease outcomes using data for 120 091 individuals from UK Biobank.Methods: We performed a phenome-wide association study (PheWAS) to identify disease outcomes associated with SUA genetic risk loci. We then implemented conventional Mendelianrandomisation (MR) analysis to investigate the causal relevance between SUA level and disease outcomes identified from PheWAS. We next applied MR Egger analysis to detect and account for potential pleiotropy, which conventional MR analysis might mistake for causality, and used the HEIDI (heterogeneity in dependent instruments) test to remove cross-phenotype associations that were likely due to genetic linkage.Results: Our PheWAS identified 25 disease groups/outcomes associated with SUA genetic risk loci after multiple testing correction (P<8.57e-05). Our conventional MR analysis implicated a causal role of SUA level in three disease groups: inflammatory polyarthropathies (OR=1.22, 95% CI 1.11 to 1.34), hypertensive disease (OR=1.08, 95% CI 1.03 to 1.14) and disorders of metabolism (OR=1.07, 95% CI 1.01 to 1.14); and four disease outcomes: gout (OR=4.88, 95% CI 3.91 to 6.09), essential hypertension (OR=1.08, 95% CI 1.03 to 1.14), myocardial infarction (OR=1.16, 95% CI 1.03 to 1.30) and coeliac disease (OR=1.41, 95% CI 1.05 to 1.89). After balancing pleiotropic effects in MR Egger analysis, only gout and its encompassing disease group of inflammatory polyarthropathies were considered to be causally associated with SUA level. Our analysis highlighted a locus (ATXN2/S2HB3) that may influence SUA level and multiple cardiovascular and autoimmune diseases via pleiotropy.Conclusions: Elevated SUA level is convincing to cause gout and inflammatory polyarthropathies, and might act as a marker for the wider range of diseases with which it associates. Our findings support further investigation on the clinical relevance of SUA level with cardiovascular, metabolic, autoimmune and respiratory diseases. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this work was to develop a rapid and robust whole-body fat-water MRI (FWMRI) method using a continuously moving table (CMT) with dynamic field corrections at 3 Tesla. Methods CMT FWMRI was developed at 3 Tesla with a multiecho golden angle (GA) radial trajectory and dynamic B0 field shimming. Whole-body imaging was performed with 4 echoes and superior-inferior coverage of 1.8 meters without shims in 90 s. 716 axial images were reconstructed with GA profile binning followed by B0 field map generation using fast three-point seeded region growing fat-water separation and slice-specific 0th and 1st order shim calculation. Slice-specific shims were applied dynamically in a repeated CMT FWMRI scan in the same session. The resulting images were evaluated for field homogeneity improvements and quality of fat-water separation with a whole-image energy optimized algorithm. Results GA sampling allowed high quality whole-body FWMRI from multiecho CMT data. Dynamic B0 shimming greatly improved field homogeneity in the body and produced high quality water and fat only images as well as fat signal fraction and R2* relaxivity maps. Conclusion A rapid and robust technique for whole-body fat-water quantification has been developed with CMT MRI with dynamic B0 field correction. Magn Reson Med 76:183-190, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Damage to specific white matter tracts within the spinal cord can often result in the particular neurological syndromes that characterize myelopathies such as traumatic spinal cord injury. Noninvasive visualization of these tracts with imaging techniques that are sensitive to microstructural integrity is an important clinical goal. Diffusion tensor imaging (DTI)- and magnetization transfer (MT)-derived quantities have shown promise in assessing tissue health in the central nervous system. In this paper, we demonstrate that DTI of the cervical spinal cord can reliably discriminate sensory (dorsal) and motor (lateral) columns. From data derived from nine healthy volunteers, two raters quantified column-specific parallel ( λ||) and perpendicular ( λ⟂) diffusivity, fractional anisotropy (FA), mean diffusivity (MD), and MT-weighted signal intensity relative to cerebrospinal fluid (MTCSF) over two time-points separated by more than 1 week. Cross-sectional means and standard deviations of these measures in the lateral and dorsal columns were as follows: λ||: 2.13 ± 0.14 and 2.14 ± 0.11 μm2/ms; λ⟂: 0.67 ± 0.16 and 0.61 ± 0.09 μm2/ms; MD: 1.15 ± 0.15 and 1.12 ± 0.08 μm2/ms; FA: 0.68 ± 0.06 and 0.68 ± 0.05; MTCSF: 0.52 ± 0.05 and 0.50 ± 0.05. We examined the variability and interrater and test-retest reliability for each metric. These column-specific MR measurements are expected to enhance understanding of the intimate structure-function relationship in the cervical spinal cord and may be useful for the assessment of disease progression. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means ± SD; 60.2 ± 7.6 vs. 62.4 ± 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 ± 11.5 vs. -74.5 ± 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.

Purpose: The purpose of this work was to develop a rapid and robust whole-body fat-water MRI (FWMRI) method using a continuously moving table (CMT) with dynamic field corrections at 3 Tesla., Methods: CMT FWMRI was developed at 3 Tesla with a multiecho golden angle (GA) radial trajectory and dynamic B0 field shimming. Whole-body imaging was performed with 4 echoes and superior-inferior coverage of 1.8 meters without shims in 90 s. 716 axial images were reconstructed with GA profile binning followed by B0 field map generation using fast three-point seeded region growing fat-water separation and slice-specific 0(th) and 1(st) order shim calculation. Slice-specific shims were applied dynamically in a repeated CMT FWMRI scan in the same session. The resulting images were evaluated for field homogeneity improvements and quality of fat-water separation with a whole-image energy optimized algorithm., Results: GA sampling allowed high quality whole-body FWMRI from multiecho CMT data. Dynamic B0 shimming greatly improved field homogeneity in the body and produced high quality water and fat only images as well as fat signal fraction and R2 * relaxivity maps., Conclusion: A rapid and robust technique for whole-body fat-water quantification has been developed with CMT MRI with dynamic B0 field correction. Magn Reson Med 76:183-190, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)