A novel multiparametric imaging approach to acute myocarditis using T2-mapping and CMR feature tracking

Background: The aim of this study was to evaluate the diagnostic potential of a novel cardiovascular magnetic resonance (CMR) based multiparametric imaging approach in suspected myocarditis and to compare it to traditional Lake Louise criteria (LLC). Methods: CMR data from 67 patients with suspected acute myocarditis were retrospectively analyzed. Seventeen age- and gender-matched healthy subjects served as control. T2-mapping data were acquired using a Gradient-Spin-Echo T2-mapping sequence in short-axis orientation. T2-maps were segmented according to the 16-segments AHA-model and segmental T2 values and pixel-standard deviation (SD) were recorded. Afterwards, the parameters maxT2 (the highest segmental T2 value) and madSD (the mean absolute deviation (MAD) of the pixel-SDs) were calculated for each subject. Cine sequences in three long axes and a stack of short-axis views covering the left and right ventricle were analyzed using a dedicated feature tracking algorithm. Results: A multiparametric imaging model containing madSD and LV global circumferential strain (GCSLV) resulted in the highest diagnostic performance in receiver operating curve analyses (area under the curve [AUC] 0.84) when compared to any model containing a single imaging parameter or to LLC (AUC 0.79). Adding late gadolinium enhancement (LGE) to the model resulted in a further increased diagnostic performance (AUC 0.93) and yielded the highest diagnostic sensitivity of 97% and specificity of 77%. Conclusions: A multiparametric CMR imaging model including the novel T2-mapping derived parameter madSD, the feature tracking derived strain parameter GCSLV and LGE yields superior diagnostic sensitivity in suspected acute myocarditis when compared to any imaging parameter alone and to LLC. © 2017 The Author(s)

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Summary Background Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10−9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10−9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10−21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.Peer reviewe

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 x 10(-13)) and African ancestries (rs2066702; P = 2.2 x 10(-9)). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.Peer reviewe

Intra- and inter-observer reproducibility of global and regional magnetic resonance feature tracking derived strain parameters of the left and right ventricle

Objectives: To investigate the reproducibility of regional and global strain and strain rate (SR) parameters of both ventricles and to determine sample sizes for all investigated strain and SR parameters in order to generate a practical reference for future studies. Materials and methods: The study population consisted of 20 healthy individuals and 20 patients with acute myocarditis. Cine sequences in three horizontal long axis views and a stack of short axis views covering the entire left and right ventricle (LV, RV) were retrospectively analysed using a dedicated feature tracking (FT) software algorithm (TOMTEC). For intra-observer analysis, one observer analysed CMR images of all patients and volunteers twice. For inter-observer analysis, three additional blinded observers analysed the same datasets once. Intra-and inter-observer reproducibility were tested in all patients and controls using Bland-Altman analyses, intra-class correlation coefficients (ICCs) and coefficients of variation. Results: Intra-observer reproducibility of global LV strain and SR parameters was excellent (range of ICCs: 0.81-1.00), the only exception being global radial SR with a poor reproducibility (ICC 0.23). On a regional level, basal and midventricular strain and SR parameters were more reproducible when compared to apical parameters. Inter-observer reproducibility of all LV parameters was slightly lower than intra-observer reproducibility, yet still good to excellent for all global and regional longitudinal and circumferential strain and SR parameters (range of ICCs: 0.66-0.93). Similar to the LV, all global RV longitudinal and circumferential strain and SR parameters showed an excellent reproducibility, (range of ICCs: 0.75-0.97). Radial strain and SR parameters were less reproducible in the LV as well as in the RV when compared to circumferential or longitudinal parameters. Conclusion: CMR FT using the TOMTEC algorithm is highly reproducible in health and disease in both, the LV and RV on a global and regional level. The only exceptions are radial strain and SR parameters, which should be used with caution within clinical studies. The sample sizes estimated on the basis of the present study might serve as a reference during the planning of future FT studies. (C) 2017 Elsevier B.V. All rights reserved

Re-evaluation of a novel approach for quantitative myocardial oedema detection by analysing tissue inhomogeneity in acute myocarditis using T2-mapping

To re-evaluate a recently suggested approach of quantifying myocardial oedema and increased tissue inhomogeneity in myocarditis by T2-mapping. Cardiac magnetic resonance data of 99 patients with myocarditis were retrospectively analysed. Thirthy healthy volunteers served as controls. T2-mapping data were acquired at 1.5 T using a gradient-spin-echo T2-mapping sequence. T2-maps were segmented according to the 16-segments AHA-model. Segmental T2-values, segmental pixel-standard deviation (SD) and the derived parameters maxT2, maxSD and madSD were analysed and compared to the established Lake Louise criteria (LLC). A re-estimation of logistic regression models revealed that all models containing an SD-parameter were superior to any model containing global myocardial T2. Using a combined cut-off of 1.8 ms for madSD + 68 ms for maxT2 resulted in a diagnostic sensitivity of 75% and specificity of 80% and showed a similar diagnostic performance compared to LLC in receiver-operating-curve analyses. Combining madSD, maxT2 and late gadolinium enhancement (LGE) in a model resulted in a superior diagnostic performance compared to LLC (sensitivity 93%, specificity 83%). The results show that the novel T2-mapping-derived parameters exhibit an additional diagnostic value over LGE with the inherent potential to overcome the current limitations of T2-mapping

Myocardial T1 and T2 mapping in severe aortic stenosis: Potential novel insights into the pathophysiology of myocardial remodelling

Purpose: Severe aortic stenosis (AS) is known to be associated with substantial myocardial remodelling, leading to diffuse myocardial fibrosis (DMF). Native myocardial T1 is emerging as a novel imaging biomarker for the non-invasive assessment of DMF. In contrast, no studies exist elucidating changes of myocardial T2 reflecting myocardial oedema in the presence of AS. The purpose of the present study was to combine native T1 and T2 mapping in order to characterize myocardial tissue changes in the setting of severe AS. Methods: After obtaining ethical approval and informed consent, a total of 26 prospectively selected patients with severe AS (13 women, mean age 81 +/- 7 years) and 17 healthy controls (12 women, mean age 63 +/- 6 years) underwent cardiac magnetic resonance (CMR) imaging on a clinical 3 T scanner. The CMR protocol included a native Modified Look-Locker (MOLLI) T1 mapping and a Gradient Spin Echo (GraSE) T2-mapping sequence in three short-axis slices and one long-axis view. After segmentation, myocardial T1 and T2 values were averaged over the entire myocardium. Statistical analysis was performed using Wilcoxon sum-rank test, Welch's independent t-test and Pearson's correlation coefficient. Results: Global native myocardial T1 was significantly increased in AS patients when compared to controls (1305 +/- 39 vs. 1272 +/- 21 ms, p = .005). Similarly, mean myocardial T2 was significantly elevated in AS patients (51 +/- 4 vs. 46 +/- 2 ms, p < .001) and showed a strong correlation with native T1 (r = .60, p < .001). An overlap was observed between T1 of both groups, whereas T2 discriminated nearly perfectly between the two groups (area under the curve in ROC analyses: 0.76 for T1, 0.87 for T2). Conclusions: Patients with severe AS exhibit significantly elevated native myocardial T1, which has previously been shown to correlate with the amount of myocardial collagen. Adding to this evidence, the present study is the first to show that native T1 and T2 are both significantly elevated and correlated in AS patients, pointing towards a potential role of oedematous/inflammatory processes in the pathophysiology of myocardial remodelling associated with AS

Precision, reproducibility and applicability of an undersampled multi-venc 4D flow MRI sequence for the assessment of cardiac hemodynamics

Background and purpose: For the assessment of cardiovascular blood flow, 2D flow (2D) and 4D flow with a single venc (4D Mono) are established techniques. The objective of this study was to validate a multi-venc 4D flow (4D Multi) sequence for the improved simultaneous assessment of arterial and venous flow in high and low flow conditions and to investigate the scan-rescan reproducibility and inter-observer variability of the novel sequence. Methods: Eleven volunteers with no known heart condition (female: 6, mean age: 25.8 +/- 9.1 years) and two patients with a Fontan circulation were examined using phase-contrast 2D and 4D flow MRI. Stroke volumes, maximum velocities, net flow curves and internal consistency were measured and compared between 2D, 4D Mono and 4D Multi. Additionally, scan-rescan and inter-observer variabilities were analyzed. Finally, qualitative visualization comparisons were performed. Results: Bland-Altman analysis show a higher agreement in stroke volumes between 4D Multi and 2D (7 +/- 11%) than 4D Mono and 2D (11 +/- 24%). 4D Multi is more accurate than 4D Mono in measuring time resolved net flow throughout the cardiac cycle and qualitative blood flow visualization of 4D Multi is more accurate in visualizing flow patterns revealing more details and less artifacts than 4D Mono. Scan-rescan reproducibility is higher in 4D Multi (-0.04 +/- 4.5 ml) than 2D (2.1 +/- 7.3 ml) and inter-observer variability is low in both techniques (2D: -0.4 +/- 3.4 ml and 4D Multi: 0.4 +/- 3.5 ml). Internal consistency was improved in volunteers and patients when using 4D Multi as compared to 4D Mono. Conclusion: 4D Multi offers a comprehensive way to accurately quantify flow in arteries and veins both in high and low flow situations and to visualize detailed flow patterns. This technique is readily applicable in the clinical setting and has the potential to be beneficial in the clinical assessment of valvular and congenital heart diseases