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Background: Youth-onset type 2 diabetes (Y-T2D) is associated with increased risk for coronary atherosclerotic disease, but the timing of the earliest pathological features and evidence of cardiac endothelial dysfunction have not been evaluated in this population. Endothelial function magnetic resonance imaging may detect early and direct endothelial dysfunction in the absence of classical risk factors (severe hyperglycemia, hypertension, and hyperlipidemia). Using endothelial function magnetic resonance imaging, we evaluated peripheral and coronary artery structure and endothelial function in young adults with Y-T2D diagnosed ≤5 years compared with age-matched healthy peers. We isolated and characterized plasma-derived small extracellular vesicles and evaluated their effects on inflammatory and signaling biomarkers in healthy human coronary artery endothelial cells to validate the imaging findings., Methods: Right coronary wall thickness, coronary artery flow-mediated dilation, and brachial artery flow-mediated dilation were measured at baseline and during isometric handgrip exercise using a 3.0T magnetic resonance imaging. Human coronary artery endothelial cells were treated with Y-T2D plasma-derived small extracellular vesicles. Protein expression was measured by Western blot analysis, oxidative stress was measured using the redox-sensitive probe dihydroethidium, and nitric oxide levels were measured by 4-amino-5-methylamino-2',7'-difluororescein diacetate., Results: Y-T2D (n=20) had higher hemoglobin A1c and high-sensitivity C-reactive protein, but similar total and LDL (low-density lipoprotein)-cholesterol compared with healthy peers (n=16). Y-T2D had greater coronary wall thickness (1.33±0.13 versus 1.22±0.13 mm; P =0.04) and impaired endothelial function: lower coronary artery flow-mediated dilation (-3.1±15.5 versus 15.9±17.3%; P <0.01) and brachial artery flow-mediated dilation (6.7±14.7 versus 26.4±15.2%; P =0.001). Y-T2D plasma-derived small extracellular vesicles reduced phosphorylated endothelial nitric oxide synthase expression and nitric oxide levels, increased reactive oxygen species production, and elevated ICAM (intercellular adhesion molecule)-mediated inflammatory pathways in human coronary artery endothelial cells., Conclusions: Coronary and brachial endothelial dysfunction was evident in Y-T2D who were within 5 years of diagnosis and did not have severe hyperglycemia or dyslipidemia. Plasma-derived small extracellular vesicles induced markers of endothelial dysfunction, which corroborated accelerated subclinical coronary atherosclerosis as an early feature in Y-T2D., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02830308 and NCT01399385., Competing Interests: None.

Objectives: Three-dimensional (3D) magnetic resonance elastography (MRE) measures liver fibrosis and inflammation but requires several breath-holds that hamper clinical acceptance. The aim of this study was to evaluate the technical and clinical feasibility of a single breath-hold 3D MRE sequence as a means of measuring liver fibrosis and inflammation in obese patients., Methods: From November 2020 to December 2021, subjects were prospectively enrolled and divided into 2 groups. Group 1 included healthy volunteers (n = 10) who served as controls to compare the single breath-hold 3D MRE sequence with a multiple-breath-hold 3D MRE sequence. Group 2 included liver patients (n = 10) who served as participants to evaluate the clinical feasibility of the single breath-hold 3D MRE sequence in measuring liver fibrosis and inflammation. Controls and participants were scanned at 60 Hz mechanical excitation with the single breath-hold 3D MRE sequence to retrieve the magnitude of the complex-valued shear modulus (|G*| [kPa]), the shear wave speed (Cs [m/s]), and the loss modulus (G" [kPa]). The controls were also scanned with a multiple-breath-hold 3D MRE sequence for comparison, and the participants had histopathology (Ishak scores) for correlation with Cs and G"., Results: For the 10 controls, 5 were female, and the mean age and body mass index were 33.1 ± 9.5 years and 23.0 ± 2.1 kg/m 2 , respectively. For the 10 participants, 8 were female, and the mean age and body mass index were 45.1 ± 16.5 years and 33.1 ± 4.0 kg/m 2 (obese range), respectively. All participants were suspected of having nonalcoholic fatty liver disease. Bland-Altman analysis of the comparison in controls shows there are nonsignificant differences in |G*|, Cs, and G" below 6.5%, suggesting good consensus between the 2 sequences. For the participants, Cs and G" correlated significantly with Ishak fibrosis and inflammation grades, respectively ( ρ = 0.95, P < 0.001, and ρ = 0.84, P = 0.002)., Conclusion: The single breath-hold 3D MRE sequence may be effective in measuring liver fibrosis and inflammation in obese patients., Competing Interests: Conflicts of interest and sources of funding: Omar Darwish is a PhD candidate, and their university tuitions fees are covered by Siemens Healthineers. Dr Radhouene Neji is an employee of Siemens Healthineers United Kingdom, Dr Daniel Stäb is an employee of Siemens Healthcare Australia, and Dr Peter Speier is an employee of Siemens Healthcare Germany. For the remaining authors, none were declared. Sources of funding: CRUK City of London Centre Award (C7893/A26233), CRUK (EDDCPGM/100001), Siemens Healthineers, ITMO Aviesan 2020 (DESP/PB n°241), National Institutes of Health intramural fund, and by US Agency for International Development (USAID) and National Academy of Sciences through Subaward 2000012771 (any opinions, findings, conclusions, or recommendations expressed are those of the authors alone, and do not necessarily reflect the views of USAID or National Academy of Sciences)., (Copyright © 2023 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Rationale: In black women, triglycerides are paradoxically normal in the presence of insulin resistance. This relationship may be explained by race-related differences in central adiposity and SCD (stearoyl-CoA desaturase)-1 enzyme activity index., Objective: In a cross-sectional study, to compare fasting and postprandial triglyceride-rich lipoprotein particle (TRLP) concentrations and size in black compared with white pre- and postmenopausal women and determine the relationship between TRLP subfractions and whole-body insulin sensitivity, hepatic and visceral fat, and SCD-1 levels., Methods and Results: In 122 federally employed women without diabetes mellitus, 73 black (58 African American and 15 African immigrant) and 49 white; age, 44±10 (mean±SD) years; body mass index, 30.0±5.6 kg/m 2 , we measured lipoprotein subfractions using nuclear magnetic resonance. Hepatic fat was measured by proton magnetic resonance spectroscopy, insulin sensitivity index calculated by minimal modeling from a frequently sampled intravenous glucose test, and red blood cell fatty acid profiles were measured by gas chromatography and were used to estimate SCD-1 indices. Hepatic fat, insulin sensitivity index, and SCD-1 were similar in black women and lower than in whites, regardless of menopausal status. Fasting and postprandial large, medium, and small TRLPs, but not very small TRLPs, were lower in black women. Fasting large, medium, and very small TRLPs negatively correlated with insulin sensitivity index and positively correlated with visceral and hepatic fat and SCD-1 activity in both groups. In multivariate models, visceral fat and SCD-1 were associated with total fasting TRLP concentrations (adjR2, 0.39; P =0.001). Black women had smaller postprandial changes in large ( P =0.005) and medium TRLPs ( P =0.007)., Conclusions: Lower visceral fat and SCD-1 activity may contribute to the paradoxical association of lower fasting and postprandial TRLP subfractions despite insulin resistance in black compared with white pre- and postmenopausal women. Similar concentrations of very small TRLPs are related to insulin resistance and could be important mediators of cardiometabolic disease risk in women., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01809288.

Objective: This study optimizes use of 3-T magnetic resonance imaging (MRI) to delineate coronary venous anatomy and compares 3-T MRI with multidetector computed tomography (MDCT) measurements., Methods: The study population included 37 consecutive subjects (22 men, 19-71 years old). Whole-heart contrast-enhanced MRI images at 3 T were acquired using segmented k-space gradient echo with inversion recovery prepared technique. The MDCT images were obtained using nonionic iodinated contrast., Results: The coronary sinus and great cardiac, posterior interventricular, and anterior interventricular veins were visualized in 100% of cases by both MRI and MDCT. Detection of the posterior vein of the left ventricle and the left marginal vein by MRI was 97% and 81%, respectively. Bland-Altman plots showed agreement in ostial diameter measured by both modalities with correlation coefficients ranging from 0.5 to 0.76. Vein length and distances also agreed closely., Conclusions: Free-breathing whole-heart 3-dimensional MRI at 3 T provides high-spatial-resolution images and could offer an alternative imaging technique instead of MDCT scans.

Purpose: The purposes of this study were to (1) develop a high-resolution 3-T magnetic resonance angiography (MRA) technique with an in-plane resolution approximate to that of multidetector coronary computed tomography (MDCT) and a voxel size of 0.35 × 0.35 × 1.5 mm³ and to (2) investigate the image quality of this technique in healthy participants and preliminarily in patients with known coronary artery disease (CAD)., Materials and Methods: A 3-T coronary MRA technique optimized for an image acquisition voxel as small as 0.35 × 0.35 × 1.5 mm³ (high-resolution coronary MRA [HRC]) was implemented and the coronary arteries of 22 participants were imaged. These included 11 healthy participants (average age, 28.5 years; 5 men) and 11 participants with CAD (average age, 52.9 years; 5 women) as identified on MDCT. In addition, the 11 healthy participants were imaged using a method with a more common spatial resolution of 0.7 × 1 × 3 mm³ (regular-resolution coronary MRA [RRC]). Qualitative and quantitative comparisons were made between the 2 MRA techniques., Results: Normal vessels and CAD lesions were successfully depicted at 350 × 350 μm² in-plane resolution with adequate signal-to-noise ratio (SNR) and contrast-to-noise ratio. The CAD findings were consistent among MDCT and HRC. The HRC showed a 47% improvement in sharpness despite a reduction in SNR (by 72%) and in contrast-to-noise ratio (by 86%) compared with the regular-resolution coronary MRA., Conclusion: This study, as a first step toward substantial improvement in the resolution of coronary MRA, demonstrates the feasibility of obtaining at 3 T a spatial resolution that approximates that of MDCT. The acquisition in-plane pixel dimensions are as small as 350 × 350 μm² with a 1.5-mm slice thickness. Although SNR is lower, the images have improved sharpness, resulting in image quality that allows qualitative identification of disease sites on MRA consistent with MDCT.

Background: Cardiac magnetic resonance imaging (CMRI) is an important tool to assess cardiac function. However, one of the limitations of CMRI is the need for frequent breath-holding (BH) steps. This may be inconvenient to some patients and limit the use of this modality in patients unable to cooperate because of cognitive reasons or physically incapable of performing the required BH steps. The purpose of this study is to overcome the intrinsic timing and computation limitations of dual-navigator cine imaging and demonstrate the feasibility of free-breathing (FB) cine cardiac left ventricular function with a single-respiratory-navigator gating at 3 T., Results: Eight participants underwent cine CMRI with both the conventional 2-dimensional cine BH and FB navigator-gated techniques. Scan parameters were identical, except in the FB technique, in which a respiratory navigator and only 2 signal averages were used. Images were scored for quality. Left ventricular end-systolic volume and end-diastolic volume were calculated. The differences in the end-systolic volume and end-diastolic volume assessed by the BH and FB were not statistically significant with P = 0.9 and 0.2, respectively. There was a good agreement between LV volumes with the limits of agreement (± 2 SD = ± 22.36 mL). Image quality score was not significantly different (P = 0.76)., Conclusions: Free-breathing cine imaging utilizing a single-respiratory-navigator gating technique is comparable to conventional BH technique in both qualitative and quantitative imaging measures. Therefore, the FB cine technique can be used as an alternative for children and patients who are unable to hold their breath.