Subclinical Changes in Cardiac Functional Parameters as Determined by Cardiovascular Magnetic Resonance (CMR) Imaging in Sleep Apnea and Snoring: Findings from UK Biobank.

Background and Objectives: Obstructive sleep apnea (OSA) is a common disorder with an increased risk for left ventricular and right ventricular dysfunction. Most studies to date have examined populations with manifest cardiovascular disease using echocardiography to analyze ventricular dysfunction with little or no reference to ventricular volumes or myocardial mass. Our aim was to explore these parameters with cardiac MRI. We hypothesized that there would be stepwise increase in left ventricular mass and right ventricular volumes from the unaffected, to the snoring and the OSA group. Materials and Methods: We analyzed cardiac MRI data from 4978 UK Biobank participants free from cardiovascular disease. Participants were allocated into three cohorts: with OSA, with self-reported snoring and without OSA or snoring (n = 118, 1886 and 2477). We analyzed cardiac parameters from balanced cine-SSFP sequences and indexed them to body surface area. Results: Patients with OSA were mostly males (47.3% vs. 79.7%; p < 0.001) with higher body mass index (25.7 ± 4.0 vs. 31.3 ± 5.3 kg/m²; p < 0.001) and higher blood pressure (135 ± 18 vs. 140 ± 17 mmHg; p = 0.012) compared to individuals without OSA or snoring. Regression analysis showed a significant effect for OSA in left ventricular end-diastolic index (LVEDVI) (ß = -4.9 ± 2.4 mL/m²; p = 0.040) and right ventricular end-diastolic index (RVEDVI) (ß = -6.2 ± 2.6 mL/m²; p = 0.016) in females and for right ventricular ejection fraction (RVEF) (ß = 1.7 ± 0.8%; p = 0.031) in males. A significant effect was discovered in snoring females for left ventricular mass index (LVMI) (ß = 3.5 ± 0.9 g/m²; p < 0.001) and in males for left ventricular ejection fraction (LVEF) (ß = 1.0 ± 0.3%; p = 0.001) and RVEF (ß = 1.2 ± 0.3%; p < 0.001). Conclusion: Our study suggests that OSA is highly underdiagnosed and that it is an evolving process with gender specific progression. Females with OSA show significantly lower ventricular volumes while males with snoring show increased ejection fractions which may be an early sign of hypertrophy. Separate prospective studies are needed to further explore the direction of causality.

Estimation of endothelial shear stress in atherosclerotic lesions detected by intravascular ultrasound using computational fluid dynamics from coronary CT scans with a pulsatile blood flow and an individualized blood viscosity.

INTRODUCTION: Endothelial shear stress (ESS) is a local hemodynamic factor that is dependent on vessel geometry and influences the process of atherogenesis. As in vivo measurements of ESS are not possible, it must be calculated using computational fluid dynamics (CFD). In this feasibility study we explore CFD-models generated from coronary CT-angiography (CCTA) using an individualised blood viscosity and a pulsatile flow profile derived from in vivo measurements. MATERIALS AND METHODS: We retrospectively recruited 25 consecutive patients who received a CCTA followed by a coronary angiography including intravascular ultrasound (IVUS) and generated 3D models of the coronary arteries from the CT-datasets. We then performed CFD-simulations on these models. Hemodynamically non-relevant stenosis were identified in IVUS. They were isolated in the CFD-model and separated longitudinally into a half with atherosclerotic lesion (AL) and one without (NAL). ESS was measured and compared for both halves. RESULTS: After excluding vessels with no IVUS data or relevant stenosis we isolated 31 hemodynamically non-relevant excentric AL from a total of 14 vessels. AL segments showed consistently significantly lower ESS when compared to their corresponding NAL segments when regarding minimum (0.9 Pa, CI [0.6, 1.2] vs. 1.3 Pa, CI [0.9, 1.8]; p = 0.004), mean (5.0 Pa, CI [3.4, 6.0] vs. 6.7 Pa, CI [5.5, 8.4]; p = 0.008) and maximum ESS values (12.4 Pa, CI [8.6, 14.6] vs. 19.6 Pa, CI [12.4, 21.0]; p = 0.005). Qualitatively ESS was lower on the inside of bifurcations and curvatures. CONCLUSION: CFD simulations of coronary arteries from CCTA with an individualised flow profile and blood viscosity are feasible and could provide further prognostic information and a better risk stratification in coronary artery disease. Further prospective studies are needed to investigate this claim.

Incidental findings in whole-body MR imaging of a population-based cohort study: Frequency, management and psychosocial consequences.

OBJECTIVES: Management of incidental findings (IF) remains controversial but highly relevant. Our aim was to assess the frequency, management and psychosocial consequences of IF reporting in a population-based cohort study undergoing whole-body MR imaging. METHODS: The study was nested in a prospective cohort from a longitudinal, population-based cohort (KORA-FF4) in southern Germany. All MR obtained on 3 T MR scanner were reviewed by board-certified radiologists regarding clinically relevant IF. A baseline and follow-up questionnaires including PHQ-9 were completed prior to and 6-month after to the scan. RESULTS: Of 400 participants (56.3 ±â€¯9.2years, 58 % male) undergoing whole-body MR, IF were found in 22 % of participants (n = 89); most frequently located in the abdominal sequences. In the pre-scan survey, most participants stated as the motivation that they wanted to "contribute to a scientific purpose" (91 %), while "knowing whether I'm healthy" was the most frequent motivation reported 6 months post-scan (88 %). The desire for IF reporting increased over time (pre- vs. 6-months-post-scan), also for clinically less important IF (72 % vs. 84 %, p = 0.001). Regarding psychosocial impact, a small portion (3.4 %) reported that awaiting the IF report added "definitely" or "very probably" additional stress burden. Of participants with reported IF, 56.8 % classified the results as "very helpful". In the post-scan survey moderate depression was observed in 3.3 % and severe depression in 1.2 %. This did not differ between participants with and without reported IF. CONCLUSION: In a cohort with whole-body MR imaging, the prevalence of IF was high. Participants considered reporting of IF highly important and added only minor psychological burden.

Measurement of total and visceral fat mass in young adult women: a comparison of MRI with anthropometric measurements with and without bioelectrical impedance analysis.

OBJECTIVE: MRI is established for measurement of body fat mass (FM) and abdominal visceral adipose tissue (VAT). Anthropometric measurements and bioelectrical impedance analysis (BIA) have been proposed as surrogates to estimation by MRI. Aim of this work is to assess the predictive value of these methods for FM and VAT measured by MRI. METHODS: Patients were selected from cohort study PPS-Diab (prediction, prevention and subclassification of Type 2 diabetes). Total FM and VAT were quantified by MRI and BIA together with clinical variables like age, waist and hip circumference and height. Least-angle regressions were utilized to select anthropometric and BIA parameters for their use in multivariable linear regression models to predict total FM and VAT. Bland-Altman plots, Pearson correlation coefficients, Wilcoxon signed-rank tests and univariate linear regression models were applied. RESULTS: 116 females with 35 ± 3 years and a body mass index of 25.1 ± 5.3 kg/m2 were included into the analysis. A multivariable model revealed weight (ß = 0.516, p < 0.001), height (ß = -0.223, p < 0.001) and hip circumference (ß = 0.156, p = 0.003) as significantly associated with total FM measured by MRI. A additional multivariable model also showed a significant predictive value of FMBIA (ß = 0.583, p < 0.001) for FM. In addition, waist circumference (ß = 0.054, p < 0.001), weight (ß = 0.016, p = 0.031) in one model and FMBIA (ß = 0.026, p = 0.018) in another model were significantly associated with VAT quantified by MRI. However, deviations reached more than 5 kg for total FM and more than 1 kg for VAT. CONCLUSION: Anthropometric measurements and BIA show significant association with total FM and VAT. ADVANCES IN KNOWLEDGE: As these measurements show significant deviations from the absolute measured values determined by MRI, MRI should be considered the gold-standard for quantification.

Magnetic Resonance-based Assessment of Myocardial 2-Dimensional Strain Using Feature Tracking: Association With Cardiovascular Risk Factors in a Population-based Cohort Free of Cardiovascular Disease.

PURPOSE: Myocardial strain analysis is a promising tool for the detection of subtle but relevant alterations of left ventricular function, also in asymptomatic subjects. Thus, we determined the feasibility of cardiac magnetic resonance-based 2D global strain analysis using feature tracking and its association with cardiovascular risk factors in a sample from the general population. MATERIALS AND METHODS: Subjects without a history of cardiocerebrovascular disease were enrolled in a substudy of the population-based KORA (Cooperative Health Research in the Region of Augsburg) cohort. In all participants with the absence of late gadolinium enhancement, longitudinal and circumferential global strains were measured on Cine SSFP imaging (TR: 29.97 ms, TE: 1.46 ms, ST: 8 mm), using a semiautomatic segmentation algorithm (CVI42, Circle, Canada). Differences in strain values according to age, sex, body mass index, hypertension, diabetes mellitus, and hyperlipidemia were derived using linear regression analysis. RESULTS: Among 360 subjects (mean age, 56.2±9.2 y, 57% male), the average global systolic radial strain was 40.1±8.2%, circumferential 19.9±2.7%, and longitudinal 19.8±3.2%. Male sex was associated with decreased global strain values, independent of the strain direction (all P<0.001). Although many cardiovascular risk factors were correlated with strain in univariate analysis, mainly waist-to-hip ratio and HbA1c remained associated with decreased radial and circumferential strains in fully adjusted models. Similarly, higher radial and circumferential strains were observed in older subjects (ß=0.14, P=0.01 and ß=0.11, P=0.04, respectively). CONCLUSIONS: Strain analysis using magnetic resonance feature tracking is feasible in population-based cohort studies and shows differences with respect to age and sex as well as an independent association with markers of metabolic syndrome.

Association of smoking and physical inactivity with MRI derived changes in cardiac function and structure in cardiovascular healthy subjects.

We aimed to investigate the association of smoking and physical exercise on ventricular function and structure, determined by cardiac magnetic resonance imaging (CMR), in subjects without known cardiovascular diseases. A total of 381 participants (median age 57 years) of the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort underwent CMR. The participants' smoking and sporting habits were measured by a questionnaire. Physical inactivity was associated with a reduction of left ventricular ejection fraction (LV-EF), stroke volume, early diastolic peak filling rate and peak ejection rate of the left ventricle as well as right ventricular stroke volume. LV-EF was reduced in subjects with almost no physical activity compared to subjects with regular physical activity (68.4%, 95%CI 66.8-70.1% vs. 70.8%, 95%CI 69.2-72.3%, p < 0,05). Smokers had lower right ventricular end-diastolic volumes (80.6 ml/m², 95%CI 76.7-84.5 ml/m²; never-smokers: 85.5 ml/m², 95%CI 82.6-88.3 ml/m²; p < 0.05) but higher extracellular volume fractions (ECV) and fibrosis volumes (34.3 ml, 95%CI 32.5-36.0 ml, vs. 31.0 ml, 95%CI 29.6-32.3 ml, p < 0.01). We conclude that asymptomatic individuals without known cardiovascular diseases show differences in cardiac function and structure depending on their physical activity and smoking habits. This underlines the importance of prevention and health education.

Hepatic fat is superior to BMI, visceral and pancreatic fat as a potential risk biomarker for neurodegenerative disease.

OBJECTIVES: Prior studies relating body mass index (BMI) to brain volumes suggest an overall inverse association. However, BMI might not be an ideal marker, as it disregards different fat compartments, which carry different metabolic risks. Therefore, we analyzed MR-based fat depots and their association with gray matter (GM) volumes of brain structures, which show volumetric changes in neurodegenerative diseases. METHODS: Warp-based automated brain segmentation of 3D FLAIR sequences was obtained in a population-based study cohort. Associations of temporal lobe, cingulate gyrus, and hippocampus GM volume with BMI and MR-based quantification of visceral adipose tissue (VAT), as well as hepatic and pancreatic proton density fat fraction (PDFFhepatic and PDFFpanc, respectively), were assessed by linear regression. RESULTS: In a sample of 152 women (age 56.2 ± 9.0 years) and 199 men (age 56.1 ± 9.1 years), we observed a significant inverse association of PDFFhepatic and cingulate gyrus volume (p < 0.05) as well as of PDFFhepatic and hippocampus volume (p < 0.05), when adjusting for age and sex. This inverse association was further enhanced for cingulate gyrus volume after additionally adjusting for hypertension, smoking, BMI, LDL, and total cholesterol (p < 0.01) and also alcohol (p < 0.01). No significant association was observed between PDFFhepatic and temporal lobe and between temporal lobe, cingulate gyrus, or hippocampus volume and BMI, VAT, and PDFFpanc. CONCLUSIONS: We observed a significant inverse, independent association of cingulate gyrus and hippocampus GM volume with hepatic fat, but not with other obesity measures. Increased hepatic fat could therefore serve as a marker of high-risk fat distribution. KEY POINTS: • Obesity is associated with neurodegenerative processes. • In a population-based study cohort, hepatic fat was superior to BMI and visceral and pancreatic fat as a risk biomarker for decreased brain volume of cingulate gyrus and hippocampus. • Increased hepatic fat could serve as a marker of high-risk fat distribution.

Association of glycemic status and segmental left ventricular wall thickness in subjects without prior cardiovascular disease: a cross-sectional study.

BACKGROUND: Left ventricular (LV) hypertrophy and changes in LV geometry are associated with increased cardiovascular mortality. Subjects with type 2 diabetes have an increased risk of such alterations in cardiac morphology. We sought to assess the association of glycemic status and LV wall thickness measured by cardiac magnetic resonance (CMR), and potential interactions of hypertension and diabetes. METHODS: CMR was performed on 359 participants from a cross-sectional study nested in a population-based cohort (KORA FF4) free of overt cardiovascular disease. Participants were classified according to their glycemic status as either control (normal glucose metabolism), prediabetes or type 2 diabetes. Segmentation of the left ventricle was defined according to the American Heart Association (AHA) 16-segment model. Measurements of wall thickness were obtained at end-diastole and analyzed by linear regression models adjusted for traditional cardiovascular risk factors. RESULTS: LV wall thickness gradually increased from normoglycemic controls to subjects with prediabetes and subjects with diabetes (8.8 ± 1.4 vs 9.9 ± 1.4 vs 10.5 ± 1.6 mm, respectively). The association was independent of hypertension and traditional cardiovascular risk factors (ß-coefficient: 0.44 mm for prediabetes and 0.70 mm for diabetes, p-values compared to controls: p = 0.007 and p = 0.004, respectively). Whereas the association of glycemic status was strongest for the mid-cavity segments, the association of hypertension was strongest for the basal segments. CONCLUSION: Abnormal glucose metabolism, including pre-diabetes, is associated with increased LV wall thickness independent of hypertension.

No Correlation of Pancreatic Fat and ß-Cell Function in Young Women With and Without a History of Gestational Diabetes.

Context: Pancreatic steatosis may contribute to ß-cell dysfunction in type 2 diabetes (T2D), but data are controversial. Women who had gestational diabetes mellitus (GDM) are at high risk for developing T2D. Objective: To examine the association of pancreatic fat content with early/first-phase insulin secretion (as markers of ß-cell function). Design: Cross-sectional analysis of a subcohort of the monocentric, prospective cohort study titled Prediction, Prevention, and Subclassification of Type 2 Diabetes. Setting: Ludwig Maximilians University Hospital, Munich, Germany. Participants: Ninety-seven women, 3 to 16 months after pregnancy [41 normoglycemic women post-GDM, 19 women post-GDM with pathological glucose metabolism, and 37 normoglycemic women after a normoglycemic pregnancy (controls)]. Main Outcome Measures: Correlation of MRI-measured pancreatic fat content with early insulin release in an oral glucose tolerance test (OGGT) [insulin increment within the first 30 minutes of the OGTT (IR30)] and first-phase insulin response (FPIR) in an intravenous glucose tolerance test (n = 65), both adjusted for insulin sensitivity index (ISI). Results: Pancreatic fat content did not correlate with IR30 and FPIR adjusted for ISI. It correlated positively with body mass index, waist circumference, liver fat, and intraabdominal fat volume. Conclusion: Pancreatic fat content does not correlate with ß-cell function in a cohort of young women with different degrees of T2D risk.

Association between abdominal adiposity and subclinical measures of left-ventricular remodeling in diabetics, prediabetics and normal controls without history of cardiovascular disease as measured by magnetic resonance imaging: results from the KORA-FF4 Study.

OBJECTIVES: Local, abdominal fat depots may be related to alterations in cardiac function and morphology due to a metabolic linkage. Thus, we aimed to determine their association with subtle cardiac changes and the potential interaction with hyperglycemic metabolic states. METHODS: Subjects from the general population and without history of cardiovascular disease were drawn from the Cooperative Health Research in the Region of Augsburg FF4 cohort and underwent 3 T cardiac and body MRI. Measures of abdominal adiposity such as hepatic proton-density fat fraction [PDFFhepatic], subcutaneous (SAT) and visceral abdominal fat (VAT) as well as established cardiac left-ventricular (LV) measures including LV remodeling index (LVCI) were derived. Associations were determined using linear regression analysis based on standard deviation normalized predictors. RESULTS: Among a total of 374 subjects (56.2 ± 9.1 years, 58% males), 49 subjects had diabetes, 99 subjects had prediabetes and 226 represented normal controls. Only subtle cardiac alterations were observed (e.g. LVCI: 1.13 ± 0.30). While SAT was not associated, increasing VAT and increasing PDFFhepatic were independently associated with increasing LVCI (ß = 0.11 and 0.06, respectively), decreasing LV end-diastolic volume (ß = - 6.70 and 3.23, respectively), and decreasing LV stroke volume (ß = - 3.91 and - 2.20, respectively). Hyperglycemic state did not modify the associations between VAT or PDFF and LV measures (interaction term: all p ≥ 0.29). CONCLUSION: In a healthy population, VAT but also PDFFhepatic were associated with subclinical measures of LV remodeling without evidence for a modifying effect of hyperglycemic state.

Phenotypic Multiorgan Involvement of Subclinical Disease as Quantified by Magnetic Resonance Imaging in Subjects With Prediabetes, Diabetes, and Normal Glucose Tolerance.

INTRODUCTION: Detailed mechanisms in the pathophysiology of diabetes disease are poorly understood, but structural alterations in various organ systems incur an elevated risk for cardiovascular events and adverse outcome. The aim of this study was to compare multiorgan subclinical disease phenotypes by magnetic resonance (MR) imaging to study differences between subjects with prediabetes, diabetes, and normal controls. MATERIALS AND METHODS: Subjects without prior cardiovascular disease were enrolled in a prospective case-control study and underwent multiorgan MR for the assessment of metabolic and arteriosclerotic alterations, including age-related white matter changes, hepatic proton density fat fraction, visceral adipose tissue volume, left ventricular remodeling index, carotid plaque, and late gadolinium enhancement. Magnetic resonance features were summarized in a phenotypic-based score (range, 0-6). Univariate, multivariate correlation, and unsupervised clustering were performed. RESULTS: Among 243 subjects with complete multiorgan MR data sets included in the analysis (55.6 ± 8.9 years, 62% males), 48 were classified as subjects with prediabetes and 38 as subjects with diabetes. The MR phenotypic score was significantly higher in subjects with prediabetes and diabetes as compared with controls (mean score, 3.00 ± 1.04 and 2.69 ± 0.98 vs 1.22 ± 0.98, P < 0.001 respectively), also after adjustment for potential confounders. We identified 2 clusters of MR phenotype patterns associated with glycemic status (P < 0.001), independent of the MR score (cluster II-metabolic specific: odds ratio, 2.49; 95% CI, 1.00-6.17; P = 0.049). DISCUSSION: Subjects with prediabetes and diabetes have a significantly higher phenotypic-based score with a distinctive multiorgan phenotypic pattern, which may enable improved disease characterization.

Subclinical changes in MRI-determined right ventricular volumes and function in subjects with prediabetes and diabetes.

OBJECTIVES: The aim of this study was to assess subclinical changes in right ventricular volumes and function in subjects with prediabetes and diabetes and controls without a history of cardiovascular disease. METHODS: Data from 400 participants in the KORA FF4 study without self-reported cardiovascular disease who underwent 3-T whole-body MRI were obtained. The right ventricle was evaluated using the short axis and a four-chamber view. Diabetes was defined according to WHO criteria. Associations between glucose tolerance and right ventricular parameters were assessed using multivariable adjusted linear regression models. RESULTS: Data from 337 participants were available for analysis. Of these, 43 (13%) had diabetes, 87 (26%) had prediabetes, and 207 (61%) were normoglycaemic controls. There was a stepwise decrease in right ventricular volumes in men with prediabetes and diabetes in comparison with controls, including right ventricular end-diastolic volume (ß = -20.4 and ß = -25.6, respectively; p ≤ 0.005), right ventricular end-systolic volume (ß = -12.3 and ß = -12.7, respectively; p ≤ 0.037) and right ventricular stroke volume (ß = -8.1 and ß = -13.1, respectively, p ≤ 0.016). We did not observe any association between prediabetes or diabetes and right ventricular volumes in women or between prediabetes or diabetes and right ventricular ejection fraction in men and women. CONCLUSIONS: This study points towards early subclinical changes in right ventricular volumes in men with diabetes and prediabetes. KEY POINTS: • MRI was used to detect subclinical changes in right ventricular parameters. • Diabetes mellitus is associated with right ventricular dysfunction. • Impairment of right ventricular volumes seems to occur predominantly in men.

Alcohol consumption, but not smoking is associated with higher MR-derived liver fat in an asymptomatic study population.

BACKGROUND: The aim of our study was to determine the relation of alcohol consumption and cigarette smoking on continuous-measured hepatic fat fraction (HFF) in a population free of cardiovascular disease. We suggested a direct correlation of alcohol consumption with HFF and increased HFF in former smokers compared to current smokers. METHODS: Data from 384 subjects (mean age: 56 years, 58% men) of a population-based cohort study (KORA) were included in a cross-sectional design. Liver fat was assessed by 3 Tesla magnetic resonance imaging (MRI) using a multi-echo Dixon sequence and T2-corrected single voxel multi-echo spectroscopy (1H-MRS). Smoking status was classified as never, former or current smoker and alcohol consumption as non-, moderate (0.1-39.9 g/day for men and 0.1-19.9 g/day for women), or heavy drinker (≥ 40 g/day for men and ≥ 20 g/day for women). Fatty liver disease was defined as HFF≥5.56%. RESULTS: Average HFF was 8.8% by 1H-MRS and 8.5% by MRI. Former smokers showed a higher HFF (MRI: ß = 2.64; p = 0.006) and a higher FLD prevalence (MRI: OR = 1.91; p = 0.006) compared to never smokers. Current smokers showed decreased odds for FLD measured by 1H-MRS after multivariable adjustment (OR = 0.37; p = 0.007) with never smoker as reference. Heavy drinking was positively associated with HFF (1H-MRS: ß = 2.99; p = 0.003) and showed highest odds for FLD (1H-MRS: OR = 3.05; p = 0.008) with non-drinker as reference. Moderate drinking showed a positive association with HFF (1H-MRS: ß = 1.54; p = 0.061 and MRI: ß = 1.75; p = 0.050). CONCLUSIONS: Our data revealed lowest odds for FLD in current smokers, moderate drinkers showing higher HFF than non-drinkers and heavy drinkers showing highest HFF and odds for FLD. These findings partly conflict with former literature and underline the importance of further studies to investigate the complex effects on liver metabolism.

Myocardial tissue characterization by contrast-enhanced cardiac magnetic resonance imaging in subjects with prediabetes, diabetes, and normal controls with preserved ejection fraction from the general population.

Aims: To characterize changes in the myocardium in subjects with prediabetes, diabetes, and healthy controls with preserved left ventricular ejection fraction (LVEF) by using cardiac magnetic resonance imaging (CMR) in a sample from the general population. Methods and results: Subjects without history of cardiovascular disease and preserved LVEF but established diabetes, prediabetes, and controls from a population-based cohort underwent contrast-enhanced CMR. Obtained parameters included left ventricular (LV) function and morphology, late gadolinium enhancement as well as T1-mapping and derivation of extracellular volume fraction (ECV) by modified Look-Locker inversion recovery for diffuse fibrosis in a subset of patients. Fibrosis volume and cell volume were calculated and LV remodelling index was calculated by dividing the LV mass by its end-diastolic volume. Among 343 subjects (56.1 ± 9.2 years, 57% males), 47 subjects were classified as diabetes, 78 as prediabetes, and 218 as controls. Haematocrit values and thus ECV parameters were available in 251 subjects. LV remodelling index was significantly higher in participants with prediabetes and diabetes, independent of body mass index (BMI), hypertension, age, and sex. ECV was decreased in subjects with prediabetes and diabetes compared with healthy controls (23.1 ± 2.4% and 22.8 ± 3.0%, both P < 0.007). In contrast, cell volume was significantly higher in subjects with prediabetes and diabetes as compared with controls (109.1 ± 23.8 and 114.9 ± 32.3 mL vs. 96.5 ± 26.9 mL, both P < 0.03, respectively). However, differences in ECV and cell volume attenuated after the adjustment for cardiometabolic risk factors, including age, sex, BMI, and hypertension. Conclusion: Subjects with prediabetes and diabetes but preserved LVEF had higher LV remodelling indices, suggesting early detectable changes in the disease process, while diffuse myocardial fibrosis appears to be less relevant at this stage.

Linearity, Bias, and Precision of Hepatic Proton Density Fat Fraction Measurements by Using MR Imaging: A Meta-Analysis.

Purpose To determine the linearity, bias, and precision of hepatic proton density fat fraction (PDFF) measurements by using magnetic resonance (MR) imaging across different field strengths, imager manufacturers, and reconstruction methods. Materials and Methods This meta-analysis was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic literature search identified studies that evaluated the linearity and/or bias of hepatic PDFF measurements by using MR imaging (hereafter, MR imaging-PDFF) against PDFF measurements by using colocalized MR spectroscopy (hereafter, MR spectroscopy-PDFF) or the precision of MR imaging-PDFF. The quality of each study was evaluated by using the Quality Assessment of Studies of Diagnostic Accuracy 2 tool. De-identified original data sets from the selected studies were pooled. Linearity was evaluated by using linear regression between MR imaging-PDFF and MR spectroscopy-PDFF measurements. Bias, defined as the mean difference between MR imaging-PDFF and MR spectroscopy-PDFF measurements, was evaluated by using Bland-Altman analysis. Precision, defined as the agreement between repeated MR imaging-PDFF measurements, was evaluated by using a linear mixed-effects model, with field strength, imager manufacturer, reconstruction method, and region of interest as random effects. Results Twenty-three studies (1679 participants) were selected for linearity and bias analyses and 11 studies (425 participants) were selected for precision analyses. MR imaging-PDFF was linear with MR spectroscopy-PDFF (R2 = 0.96). Regression slope (0.97; P < .001) and mean Bland-Altman bias (-0.13%; 95% limits of agreement: -3.95%, 3.40%) indicated minimal underestimation by using MR imaging-PDFF. MR imaging-PDFF was precise at the region-of-interest level, with repeatability and reproducibility coefficients of 2.99% and 4.12%, respectively. Field strength, imager manufacturer, and reconstruction method each had minimal effects on reproducibility. Conclusion MR imaging-PDFF has excellent linearity, bias, and precision across different field strengths, imager manufacturers, and reconstruction methods. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on October 2, 2017.

Qualitative and Quantitative Evaluation of Structural Myocardial Alterations by Grating-Based Phase-Contrast Computed Tomography.

OBJECTIVES: Grating-based phase-contrast computed tomography (gb-PCCT) relies on x-ray refraction instead of absorption to generate high-contrast images in biological soft tissue. The aim of this study was to evaluate the potential of gb-PCCT for the depiction of structural changes in heart disease. MATERIALS AND METHODS: Four human heart specimens from patients with hypertensive disease, ischemic disease, dilated heart disease, and cardiac lipomatosis were examined. The gb-PCCT setup consisted of an x-ray tube (40 kV, 70 mA), grating-interferometer, and detector, and allowed simultaneous acquisition of phase- and absorption-contrast data. With histopathology as the standard of reference, myocardium (MC), fibrotic scar (FS), interstitial fibrosis (IF), and fatty tissue (FT) were visually and quantitatively evaluated. Systematic differences in absorption- and phase-contrast Hounsfield units (HUabs and HUp) were assessed. RESULTS: Thirteen corresponding cross-sections were included, and MC, FS, IF, and FT were found in 13 (100%), 4 (30.8%), 7 (53.8%), and 13 (100%) cross-sections, respectively. Mean HUp/HUabs were 52.5/54.1, 86.6/69.7, 62.4/62.3, and -38.6/-258.9 for MC, FS, IF, and FT, respectively. An overlap in HUabs was observed for MC and IF (P = 0.84) but not for HUp (P < 0.01). Contrast-to-noise ratios were significantly higher in phase- than in absorption-contrast for MC/FT (35.4 vs 7.8; P < 0.01) and for MC/FS (12.3 vs 0.2; P < 0.01). CONCLUSIONS: Given its superior soft tissue contrast, gb-PCCT is able to depict structural changes in different cardiomyopathies, which can currently not be obtained by x-ray absorption-based imaging methods. If current technical limitations can be overcome, gb-PCCT may evolve as a powerful tool for the anatomical assessment of cardiomyopathy.

Lack of association of MRI determined subclinical cardiovascular disease with dizziness and vertigo in a cross-sectional population-based study.

OBJECTIVE: We investigated the association between subclinical cardiovascular diseases assessed by MRI examination and symptoms of dizziness and vertigo in participants of a population-based sample. METHODS: Data from 400 participants (169 women) aged from 39 to 73 of a cross-sectional MRI sub-study of the "Kooperative Gesundheitsforschung in der Region Augsburg" (KORA) FF4 study from the south of Germany was used. MRI determined subclinical cardiovascular diseases include left and right ventricular structure and function as well as the presence of carotid plaque and carotid wall thickness. Cerebrum diseases include white matter lesions (WML) and cerebral microbleeds (CMB). The main outcomes of dizziness and vertigo were assessed by standardized interview. Logistic regression models were applied and adjusted odds ratios (OR) with 95% confidence intervals (CI) were provided. RESULTS: Lifetime and 12-month prevalence of dizziness and vertigo were 30% (95%CI 26% to 35%) and 21% (95%CI 17% to 26%) respectively in this sample. On multivariable analysis, cardiac and carotid measurements were not associated with dizziness and vertigo excluding orthostatic vertigo (20%, 95CI 16% to 24%). Only in male participants, there was a significant association between WML and the presence of dizziness and vertigo (OR = 2.95, 95%CI 1.08 to 8.07). There was no significant association of CMB with dizziness and vertigo. However, CMB and WML were tending to associate with a higher risk of dizziness and vertigo in the whole sample (CMB: OR = 1.48, 95%CI 0.70; 3.15; WML: OR = 1.71, 95%CI 0.80 to 3.67;), in persons with prediabetes and diabetes (WML: OR = 2.71, 95%CI 0.89 to 8.23) and in men with normal glucose metabolism (CMB: OR = 2.60, 95%CI 0.56 to 12.0; WML: OR = 3.08, 95%CI 0.58 to 16.5). CONCLUSIONS: In this sample of participants without manifest cardiovascular diseases, subclinical left and right ventricular function and carotid structure were consistently not associated with dizziness and vertigo. Subclinical cerebrum measurements, however, tend to increase the risk for dizziness and vertigo, especially in men and in persons with prediabetes or diabetes.

Dark-field imaging in coronary atherosclerosis.

OBJECTIVES: Dark-field imaging based on small angle X-ray scattering has been shown to be highly sensitive for microcalcifications, e.g. in breast tissue. We hypothesized (i) that high signal areas in dark-field imaging of atherosclerotic plaque are associated with microcalcifications and (ii) that dark-field imaging is more sensitive for microcalcifications than attenuation-based imaging. METHODS: Fifteen coronary artery specimens were examined at an experimental set-up consisting of X-ray tube (40kV), grating-interferometer and detector. Tomographic dark-field-, attenuation-, and phase-contrast data were simultaneously acquired. Histopathology served as standard of reference. To explore the potential of dark field imaging in a full-body CT system, simulations were carried out with spherical calcifications of different sizes to simulate small and intermediate microcalcifications. RESULTS: Microcalcifications were present in 10/10 (100%) cross-sections with high dark-field signal and without evidence of calcifications in attenuation- or phase contrast. In positive controls with high signal areas in all three modalities, 10/10 (100%) cross-sections showed macrocalcifications. In negative controls without high signal areas, no calcifications were detected. Simulations showed that the microcalcifications generate substantially higher dark-field than attenuation signal. CONCLUSIONS: Dark-field imaging is highly sensitive for microcalcifications in coronary atherosclerotic plaque and might provide complementary information in the assessment of plaque instability.

Pancreatic fat content by magnetic resonance imaging in subjects with prediabetes, diabetes, and controls from a general population without cardiovascular disease.

BACKGROUND/OBJECTIVE: Despite the relevance of pancreatic fat content in the development of metabolic diseases, its association with impaired glucose metabolism, diabetes, and other adipose tissue compartments remains unclear. Thus, we determined differences in pancreatic fat content by magnetic resonance imaging (MRI) between subjects with prediabetes, diabetes, and normal controls in a cohort from the general population. METHODS: Subjects without history of cardiovascular disease with established diabetes or prediabetes as well as normal controls were included and underwent whole-body MRI on a 3T scanner. Pancreatic fat content was quantified by measuring the proton-density fat fraction (PDFFpanc) using a 3D multi-echo GRE sequence (increment: 1.23 ms, 6 echoes) by placing ROIs in the pancreatic head, body, and tail by independent readers. In addition, hepatic fat content as well as abdominal subcutaneous and visceral adipose tissue (SAT and VAT) were measured by multi-echo GRE and 3D 2-point volume-interpolated DIXON MRI, respectively. Univariate and multivariate analyses were employed to determine associations. RESULTS: A total of 385 subjects were included in the analysis (median age: 57 years, 58.2% males), of them 53 were classified as subjects with diabetes, 95 as prediabetes, and 237 as controls (13.8%, 24.7%, and 61.6%; respectively). The median PDFFpanc was 5.2% [IQR 3.3-9.4], and significantly higher in subjects with prediabetes and diabetes as compared to controls (PDFFpanc: 6.2% [IQR: 3.5-12] vs. 8.6% [IQR: 4.3-17.5] vs. 4.9% [3.1-7.4], p<0.001, respectively). After adjusting for age, gender and BMI the association was attenuated (all p>0.12). While in univariate analysis BMI, PDFFhepatic, SAT and VAT were associated with PDFFpanc (all p<0.05), only VAT predicted PDFFpanc independently (ß: 0.02, 95%-confidence interval: 0.01-0.04, p<0.001). CONCLUSION: While pancreatic fat content differs significantly between subjects with prediabetes, diabetes and controls, this association may be confounded by age, gender, and the amount of VAT in this cross-sectional study.

Increase of Intra-abdominal Adipose Tissue in Pediatric Crohn Disease.

BACKGROUND AND OBJECTIVE: Recent evidence points toward an active immunological role of intra-abdominal adipose tissue in Crohn disease (CD). We quantified the abdominal adipose tissue compartments using magnetic resonance imaging (MRI) in 27 pediatric patients with CD compared with 14 controls undergoing MRI examination for other reasons. METHODS: Total (TAAT), subcutaneous (SCAT) and intra-abdominal (IAAT) adipose tissue areas were measured by semiautomatic segmentation on a transverse slice centered on the umbilicus (mean ±â€Šstandard deviation in square centimeter) using standard T1-weighted sequences. IAAT/TAAT and IAAT/height ratios were calculated and analyzed for associations with disease duration, phenotype, or therapy. RESULTS: Patients with CD (median age 15.0 years, range 7.7-17.9, 18/27 boys, median disease duration 29 months, range 0-136) compared to controls (median age 13.9 years, range 3.3-17.8, 4/14 boys) had higher IAAT area (42.3 ±â€Š21.0 vs 28.7 ±â€Š11.6, P = 0.0494) but similar SCAT and TAAT areas (104.6 ±â€Š72.8 vs 96.5 ±â€Š50.8, P = 0.8170 and 146.9 ±â€Š87.3 vs 125.3 ±â€Š61.5, P = 0.7417, respectively). IAAT/TAAT ratio was higher in patients with CD compared to controls (0.32 ±â€Š0.10 vs 0.24 ±â€Š0.04, P = 0.0081). Patients with disease duration >2 years (n = 14) had higher IAAT/TAAT ratio than those with shorter disease and controls (0.35 ±â€Š0.10 vs 0.28 ±â€Š0.08, P = 0.0288 and 0.24 ±â€Š0.04, P = 0.0009, respectively). In these patients, increased IAAT/height ratio was associated with complicated disease (P = 0.043, r = 0.573). No association was found between IAAT/TAAT ratio and actual disease activity or therapy. CONCLUSIONS: IAAT is increased in pediatric CD and correlates with disease duration. Assessment of IAAT accumulation may be considered in future MRI scores for inflammation and bowel damage in CD and during follow-up of different therapeutic interventions.