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Young adults with type 2 diabetes (T2D-Y) have increased risk of subclinical atherosclerotic cardiovascular disease (ASCVD) . Cardiac magnetic resonance imaging (MRI) may guide risk stratification by noninvasively quantifying coronary wall thickness (CWT, an indicator of ASCVD) and endothelial function (arterial dilation during isometric hand grip exercise, IHE) . The utility of these novel MRI biomarkers in T2D-Y is unknown. We hypothesized that T2D-Y would be associated with increased CWT and impaired endothelial function. In T2D-Y (6 male, age 19.8±1.6y, BMI 37±7kg/m2) and 12 healthy controls (5 male, age 22.7±2.9 y, BMI 24±5 kg/m2) we measured CWT and coronary and brachial dilation during IHE with a 3.0 Tesla MRI. T2D-Y had higher HbA1c (6.5 ± 0.8 vs. 5.1 ± 0.6%, P Disclosure A. Villalobos-Perez: None. J. Feeley: None. K.Z. Abd-Elmoniem: None. K.B. Dietsche: None. J.R. Matta: None. M.S. Stagliano: None. L. Mabundo: None. E.L. Shouppe: None. M. Walter: None. S.T. Chung: None. Funding NIDDK/NIH Intramural Research Program

Background Assessment of regional myocardial function at native pixel-level resolution can play a crucial role in recognizing the early signs of the decline in regional myocardial function. Extensive data processing in existing techniques limits the effective resolution and accuracy of the generated strain maps. The purpose of this study is to compute myocardial principal strain maps e p 1 and e p 2 from tagged MRI (tMRI) at the native image resolution using deep-learning local patch convolutional neural network (CNN) models (DeepStrain). Methods For network training, validation, and testing, realistic tMRI datasets were generated and consisted of 53,606 cine images simulating the heart, the liver, blood pool, and backgrounds, including ranges of shapes, positions, motion patterns, noise, and strain. In addition, 102 in-vivo image datasets from three healthy subjects, and three Pulmonary Arterial Hypertension patients, were acquired and used to assess the network's in-vivo performance. Four convolutional neural networks were trained for mapping input tagging patterns to corresponding ground-truth principal strains using different cost functions. Strain maps using harmonic phase analysis (HARP) were obtained with various spectral filtering settings for comparison. CNN and HARP strain maps were compared at the pixel level versus the ground-truth and versus the least-loss in-vivo maps using Pearson correlation coefficients (R) and the median error and Inter-Quartile Range (IQR) histograms. Results CNN-based local patch DeepStrain maps at a phantom resolution of 1.1mm × 1.1 mm and in-vivo resolution of 2.1mm × 1.6 mm were artifact-free with multiple fold improvement with e p 1 ground-truth median error of 0.009(0.007) vs. 0.32(0.385) using HARP and e p 2 ground-truth error of 0.016(0.021) vs. 0.181(0.08) using HARP. CNN-based strain maps showed substantially higher agreement with the ground-truth maps with correlation coefficients R > 0.91 for e p 1 and e p 2 compared to R Conclusion CNN-generated Eulerian strain mapping permits artifact-free visualization of myocardial function at the native image resolution.

Background Activation of brown adipose tissue (BAT) in rodents increases lipolysis in white adipose tissue (WAT) and improves glucose tolerance. Adult humans can have metabolically active BAT. Implications for diabetes and obesity in humans require a better characterization of BAT in humans. Purpose To study fat depots with localized proton MR spectroscopy relaxometry and to identify differences between WAT and fluorine 18 fluorodeoxyglucose (FDG) PET/CT proven cold-activated BAT in humans. Materials and Methods Participants were consecutively enrolled in this prospective study (ClinicalTrials.gov identifiers: NCT01568671 and NCT01399385) from August 2016 to May 2019. Supraclavicular potential BAT regions were localized with MRI. Proton densities, T1, and T2 were measured with localized MR spectroscopy in potential BAT and in subcutaneous WAT. FDG PET/CT after cold stimulation was used to retrospectively identify active supraclavicular BAT or supraclavicular quiescent adipose tissue (QAT) regions. MR spectroscopy results from BAT and WAT were compared with grouped and paired tests. Results Of 21 healthy participants (mean age, 36 years ± 16 [standard deviation]; 13 men) FDG PET/CT showed active BAT in 24 MR spectroscopy-targeted regions in 16 participants (eight men). Four men had QAT. The T2 for methylene protons was shorter in BAT (mean, 69 msec ± 6, 24 regions) than in WAT (mean, 83 msec ± 3, 18 regions, P < .01) and QAT (mean, 78 msec ± 2, five regions, P < .01). A T2 cut-off value of 76 msec enabled the differentiation of BAT from WAT or QAT with a sensitivity of 85% and a specificity of 95%. Densities of protons adjacent and between double bonds were 33% and 24% lower, respectively, in BAT compared with those in WAT (P = .01 and P = .03, respectively), indicating a lower content of unsaturated and polyunsaturated fatty acids, respectively, in BAT compared with WAT. Conclusion Proton MR spectroscopy showed shorter T2 and lower unsaturated fatty acids in brown adipose tissue (BAT) than that in white adipose tissue in healthy humans. It was feasible to identify BAT with MR spectroscopy without the use of PET/CT or cold stimulation. © RSNA, 2021 See also the editorial by Barker in this issue. Online supplemental material is available for this article.

BACKGROUND Persons living with HIV (PLWH) are at an increased risk of myocardial dysfunction and metabolic disturbances represent one of several potential contributing factors. Adiponectin is an adipokine that enhances insulin sensitivity with potential cardioprotective effects. We therefore investigated the relationship between myocardial fibrosis, adiponectin, and related metabolic parameters to better understand the pathophysiologic mechanisms of myocardial injury in PLWH. METHODS This is a prospective, cross-sectional study of PLWH without known cardiovascular disease (n = 87) and 28 healthy matched controls. Diffuse myocardial fibrosis and epicardial adipose tissue (EAT) were evaluated using cardiac magnetic resonance imaging and cardiac computed tomography. RESULTS Myocardial fibrosis was increased in PLWH and was correlated with adiponectin (r = 0.26, P = 0.004) and EAT (r = -0.42, P < 0.0001). Myocardial fibrosis was not associated with smoking pack years or CD4/CD8 ratio. In multivariate analysis that included body mass index, HIV status (P = 0.04), female sex (P < 0.0001), higher adiponectin (P = 0.046) and lower EAT (P = 0.01) were independently associated with myocardial fibrosis. CONCLUSION We describe a novel association between serum adiponectin and subclinical intramyocardial fibrosis, as well as a significant inverse relationship between intramyocardial fibrosis and EAT. Adiponectin may represent a target for preventing myocardial injury in the future; however, our findings reflect the complexity of the metabolic interactions of adiponectin and epicardial adipose as factors associated with the myocardial architecture.

PurposeAdults with Turner syndrome (TS) have an increased predisposition to ischemic heart disease. The quantitative relationship between coronary atherosclerosis and TS has yet to be established.MethodsA total of 128 females (62 with TS) participated in this prospective study. Coronary computed tomography angiography was performed to measure coronary calcified plaque burden, and prevalent noncalcified plaque burden. Regression analysis was used to study the effects of TS and traditional cardiovascular disease risk factors on coronary plaque burden.ResultsAdults with TS were 63% more likely to have coronary calcifications than controls (odds ratio 1.63, 95% confidence interval: 1.02, 2.61, P = 0.04), with an age cutoff of 51.7 years for a probability of50% for the presence of coronary calcifications, when compared to 55.7 years in female controls. The average age of TS patients with calcified plaques was significantly lower than that of controls with calcified plaques (51.5 ± 8.9 years vs. 60.5 ± 7.0 years, P 0.001). Age increased the likelihood of coronary calcifications by 13% per year (odds ratio 1.13, confidence interval 95%: 1.07-1.19, P 0.001).ConclusionThis study demonstrates a higher prevalence and earlier onset of calcified coronary plaques in TS. These findings have important implications for cardiovascular risk assessment and the management of patients with TS.

Background: Current guidelines for the primary prevention of atherosclerotic cardiovascular disease are based on the estimation of a predicted 10-year cardiovascular disease risk and the average relative risk reduction estimates from statin trials. In the clinical setting, however, decision-making is better informed by the expected benefit for the individual patient, which is typically lacking. Consequently, a personalized statin benefit approach based on absolute risk reduction over 10 years (ARR10 benefit threshold ≥2.3%) has been proposed as a novel approach. However, how this benefit threshold relates with coronary plaque burden in asymptomatic individuals with low/intermediate cardiovascular disease risk is unknown. Aims: In this study, we compared the predicted ARR10 obtained in each individual with plaque burden detected by coronary computed tomography angiography. Methods and Results: Plaque burden (segment volume score, segment stenosis score, and segment involvement score) was assessed in prospectively recruited asymptomatic subjects (n = 70; 52% male; median age 56 years [interquartile range 51–64 years]) with low/intermediate Framingham risk score (< 20%). The expected ARR10 with statin in the entire cohort was 2.7% (1.5–4.6%) with a corresponding number needed to treat over 10 years of 36 (22–63). In subjects with an ARR10 benefit threshold ≥2.3% (vs. < 2.3%), plaque burden was significantly higher (p = 0.02). Conclusion: These findings suggest that individuals with higher coronary plaque burden are more likely to get greater benefit from statin therapy even among asymptomatic individuals with low cardiovascular risk.

Context: Cushing Syndrome (CS) is characterized by cortisol excess, impaired glucose tolerance, and obesity. As assessed by CT imaging, 20% of CS patients develop steatohepatitis (NASH). The gold standard test, liver biopsy, is associated with CS complications and cannot be used to confirm the diagnosis. This study evaluated the ability of magnetic resonance spectroscopy (MRS). Objective: To identify the prevalence of NASH and its temporal changes in relation to other metabolic parameters in CS before and after successful treatment. Primary Outcome Measure: PDFF measured by MRS at 3T before, 6 and 12 months after Cushing’s syndrome treatment DESIGN: In this prospective IRB-approved study, 41 consecutive CS patients (44±1.8 y; 34(85%) females, 32.6±1.5 kg/m²; urine cortisol excretion 2242.7±1806.3 [3.5–45.0 mcg/24h]) underwent MRS before, 6 and 12months after successful treatment. PDFF was measured by MRS at 3T; NASH was defined as >5% PDFF. Metabolic markers – glycohemoglobin (A1C) and body mass index (BMI) – were measured; Wilcoxon matched-pairs signed-rank test evaluated changes over time, and spearman rank test evaluated the correlation between variables. Results: At baseline, mean PDFF was 10.4±1.7 and correlated positively with BMI (r=0.5710, p Conclusions: MRS-PDFF is valuable for diagnosing NASH in Cushing Syndrome, which can affect a third of this patient population. Liver fat decreases by 6 months after normalization of cortisol and precedes the improvement of A1C. Indicating that liver insulin resistance due to fat accumulation has an essential role in diabetes pathophysiology in CS.

Coronary plaque burden measured by coronary computerized tomography angiography (CCTA), independent of stenosis, is a significant independent predictor of coronary heart disease (CHD) events and mortality. Hence, it is essential to develop comprehensive CCTA plaque quantification beyond existing subjective plaque volume or stenosis scoring methods. The purpose of this study is to develop a framework for automated 3D segmentation of CCTA vessel wall and quantification of atherosclerotic plaque, independent of the amount of stenosis, along with overcoming challenges caused by poor contrast, motion artifacts, severe stenosis, and degradation of image quality. Vesselness, region growing, and two sequential level sets are employed for segmenting the inner and outer wall to prevent artifact-defective segmentation. Lumen and vessel boundaries are joined to create the coronary wall. Curved multiplanar reformation is used to straighten the segmented lumen and wall using lumen centerline. In-vivo evaluation included CCTA stenotic and non-stenotic plaques from 41 asymptomatic subjects with 122 plaques of different characteristics against the individual and consensus of expert readers. Results demonstrate that the framework segmentation performed robustly by providing a reliable working platform for accelerated, objective, and reproducible atherosclerotic plaque characterization beyond subjective assessment of stenosis; can be potentially applicable for monitoring response to therapy.

PURPOSE: To demonstrate the association between coronary vessel wall thickness (VWT) measured at MRI and coronary artery disease (CAD) risk in asymptomatic groups at low and intermediate risk on the basis of Framingham score. MATERIALS AND METHODS: A total of 131 asymptomatic adults were prospectively enrolled. All participants underwent CT angiography for scoring CAD, and coronary VWT was measured at 3.0-T MRI. Nonlinear single and multivariable regression analyses with consideration for interaction with sex were performed to investigate the association of traditional atherosclerotic risk factors and VWT with CT angiography–based CAD scores. RESULTS: The analysis included 62 women and 62 men with low or intermediate Framingham score of less than 20%. Age (mean age, 45.0 years ± 14.5 [standard deviation]) and body mass index were not different between the groups. Age, sex, and VWT were individually significantly associated with all CT angiography–based CAD scores (P < .05). Additionally, sex was a significant effect modifier of the associations with all CAD scores. In men, age was the only statistically significant independent risk factor of CAD; in women, VWT was the only statistically significant independent surrogate associated with increased CAD scores (P < .05). CONCLUSION: In asymptomatic women, VWT MRI was the primary independent surrogate of CAD, whereas age was the strongest risk factor in men. This study suggests that VWT may be used as a CAD surrogate in women at low or intermediate risk of CAD. Further longitudinal studies are required to determine the potential implication and use of this MRI technique for the preventative management of CAD in women. © RSNA, 2019

With access to effective combination antiretroviral therapy (ART), life expectancy of individuals with human immunodeficiency virus (HIV) is now approaching population norms [1]. Individuals who acquired HIV in early life represent the first generation of young adults growing up with lifelong exposure to HIV and ART. Long-term HIV and ART exposure are associated with elevated risks for non-AIDS-related complications, including metabolic abnormalities, and increased cardiovascular disease (CVD) risk [2]. The etiology of CVD risk in young adults with perinatal HIV infection is likely multifactorial. Chronic inflammation, aberrant immune activation, toxicity due to ART, and viral effects of HIV, in addition to traditional CVD risk factors, may contribute to increased CVD associated with HIV [3]. The relative impact of these risk factors on CVD in this population remains unknown. The diagnosis of CVD typically occurs much later in life; thus, recent research has focused on the use of diagnostic imaging to evaluate subclinical alterations in cardiovascular structure and function in younger HIV-infected populations. Although investigations have been performed using ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI), these studies focused primarily on larger vessels that may not relate directly to the heart and coronary arteries. Studies that directly interrogated the coronary arteries utilized lumenography methods via multidetector coronary CT angiography (CCTA) in older patients with additional risk factors [4, 5]. To date, direct evaluation of the coronary vessel wall using the validated novel technique of phase-sensitive black-blood MRI [6, 7] has not been conducted in a younger HIV-infected population. Accurately imaging early indicators of coronary arterial disease, including vessel wall thickening and CT quantification of discrete coronary plaque, may shed insight into the effects of HIV and/or long-term ART exposure in young adults with lifelong HIV infection. This younger population is less affected by the cumulative consequences of traditional CVD risk on the coronary arteries. The goal of this study was to assess early signs of coronary vascular disease in asymptomatic young adults with lifelong HIV infection compared with healthy controls using CT angiography and coronary vessel wall MRI. Further, we evaluated whether HIV-related factors and traditional CVD risk factors are associated with subclinical CVD in this cohort.

The purpose of this study was to (a) investigate the image quality of phase-sensitive dual-inversion recovery (PS-DIR) coronary wall imaging in healthy subjects and in subjects with known coronary artery disease (CAD) and to (b) investigate the utilization of PS-DIR at 3T in the assessment of coronary artery thickening in subjects with asymptomatic but variable degrees of CAD.A total of 37 subjects participated in this institutional review board-approved and HIPAA-compliant study. These included 21 subjects with known CAD as identified on multidetector computed tomography angiography (MDCT). Sixteen healthy subjects without known history of CAD were included. All subjects were scanned using free-breathing PS-DIR magnetic resonance imaging (MRI) for the assessment of coronary wall thickness at 3T. Lumen-tissue contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR) and quantitative vessel parameters including lumen area and wall thickness were measured. Statistical analyses were performed.PS-DIR was successfully completed in 76% of patients and in 88% of the healthy subjects. Phase-sensitive signed-magnitude reconstruction, compared to modulus-magnitude images, significantly improved lumen-tissue CNR in healthy subjects (26.73±11.95 vs. 14.65±9.57, P.001) and in patients (21.45±7.61 vs. 16.65±5.85, P.001). There was no difference in image CNR and SNR between groups. In arterial segments free of plaques, coronary wall was thicker in patients in comparison to healthy subjects (1.74±0.27 mm vs. 1.17±0.14 mm, P.001), without a change in lumen area (4.51±2.42 mm2 vs. 5.71±3.11mm2, P=.25).This is the first study to demonstrate the feasibility of successfully obtaining vessel wall images at 3T using PS-DIR in asymptomatic patients with known variable degrees of CAD as detected by MDCT. This was achieved with a fixed subject-invariant planning of blood signal nulling. With that limitation alleviated, PS-DIR coronary wall MRI is capable of detecting arterial thickening and positive arterial remodeling at 3T in asymptomatic CAD.

Observational studies show that glucocorticoid therapy and the endogenous hypercortisolism of Cushing's syndrome (CS) are associated with increased rates of cardiovascular morbidity and mortality. However, the causes of these findings remain largely unknown.To determine whether CS patients have increased coronary atherosclerosis.A prospective case-control study was performed.Subjects were evaulated in a clinical research center.Fifteen consecutive patients with ACTH-dependent CS, 14 due to an ectopic source and 1 due to pituitary Cushing's disease were recruited. Eleven patients were studied when hypercortisolemic; 4 patients were eucortisolemic due to medication (3) or cyclic hypercortisolism (1). Fifteen control subjects with at least one risk factor for cardiac disease were matched 1:1 for age, sex, and body mass index.Agatston score a measure of calcified plaque and non-calcified coronary plaque volume were quantified using a multidetector CT (MDCT) coronary angiogram scan. Additional variables included fasting lipids, blood pressure, history of hypertension or diabetes, and 24-hour urine free cortisol excretion.CS patients had significantly greater noncalcified plaque volume and Agatston score (noncalcified plaque volume [mm(3)] median [interquartile ranges]: CS 49.5 [31.4, 102.5], controls 17.9 [2.6, 25.3], P.001; Agatston score: CS 70.6 [0, 253.1], controls 0 [0, 7.6]; P.05). CS patients had higher systolic and diastolic blood pressures than controls (systolic: CS 143 mm Hg [135, 173]; controls, 134 [123, 136], P.02; diastolic CS: 86 [80, 99], controls, 76 [72, 84], P.05).Increased coronary calcifications and noncalcified coronary plaque volumes are present in patients with active or previous hypercortisolism. Increased atherosclerosis may contribute to the increased rates of cardiovascular morbidity and mortality in patients with glucocorticoid excess.

Background Non-calcified coronary artery plaque (NCAP) might be an important predictor of cardiovascular events; however, few studies have directly measured NCAP in HIV-infected individuals. Methods We completed a prospective cross-sectional evaluation of NCAP and coronary calcium scores using computed tomography angiography in HIV-infected patients ( n=26) without known coronary artery disease (CAD), but who had one or more CAD risk factor(s), and compared them with controls matched on age, race, sex, body mass index and Framingham Risk Score ( n=26). Results There was no difference in coronary calcium scores (114 ±218 versus 124 ±298; P=0.89) or NCAP volume (65 ±86 mm3 versus 63 ±82 mm3; P=0.38) between HIV-infected patients and controls, respectively. Among HIV-infected patients, lower CD4+ T-cell count was associated with increased NCAP volume ( r=-0.52, P=0.006). The CD4+ T-cell count remained a significant predictor of NCAP in a multivariate analysis that adjusted for age and duration of antiretroviral therapy. Conclusions Plaque burden is similar between HIV-infected and uninfected individuals when matched on traditional CAD risk factors; however, immune function might mediate the development of atherosclerosis in HIV infection.

Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency caused by autosomal dominant STAT3 mutations resulting in recurrent infections and connective tissue abnormalities. Coronary artery abnormalities have been reported infrequently. We aimed to determine the frequency and characteristics of coronary artery abnormalities. STAT3-mutated HIES patients (n = 38), ranging in age from 8 to 57 years, underwent coronary artery imaging by computed tomography or magnetic resonance imaging. Images were evaluated for tortuosity, dilation, and aneurysm. Charts were reviewed for cardiac risk factors. To allow blinded image interpretation, an age- and gender-matched non-HIES group was also evaluated (n = 33). Coronary artery tortuosity or dilation occurred in 70% of HIES patients, with aneurysms present in 37%, incidences much higher than in the literature and in our non-HIES group, in which 21% had tortuosity or dilation and 3% had aneurysms. Hypertension was more common in the HIES group than in the general population and was associated with vessel abnormalities. Atherosclerosis was uncommon and mild. Coronary artery aneurysms and tortuosity are common in HIES, despite a paucity of atherosclerosis, suggesting that STAT3 plays an integral role in human vascular remodeling and atherosclerosis.

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.

SummaryIntroduction Aortic abnormalities contribute to increased morbidity and mortality of women with Turner syndrome (TS). Impaired aortic stiffness may prove to have clinical prognostic value in TS as is the case in other diseases such as Marfan syndrome, diabetes and hypertension. Additionally, the parental origin of the X chromosome in TS may influence aortic stiffness. Objective To assess the relation between X chromosome parental origin and aortic stiffness in TS patients. Methods Twenty-four subjects with TS participated in this cross-sectional study at a tertiary care centre. The parental origin of the X chromosome was determined. Cardiac-gated multidetector computerized tomography (MDCT) was performed and distensibility of the ascending aorta (AA), a measure of aortic stiffness, was calculated. Results Fourteen women were Xm (maternal origin) and 10 were Xp (paternal origin) for their inheritance of the single X chromosome. Age, body size, blood pressure and AA areas were similar in the two groups. However, the calculated AA distensibility was significantly lower in the Xm group (2·8 ± 1·1 mm/Hg) than in the Xp group (4·1 ± 1·5 mm/Hg); P

Turner syndrome is the most common chromosomal abnormality in female subjects, affecting 1 in 2000 live births. The condition is associated with a generalized vasculopathy as well as congenital cardiac and other defects. We report aneurysmal dilation of medium caliber arteries involving the celiac axis and coronary vessels in two women with Turner syndrome.