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Background: Partial lipodystrophy (PL) syndromes involve deficiency of adipose tissue, causing severe insulin resistance and hypertriglyceridemia. Apolipoprotein C-III (apoC-III) is elevated in PL and is thought to contribute to hypertriglyceridemia by inhibiting lipoprotein lipase (LPL)., Objective: We hypothesized that volanesorsen, an antisense oligonucleotide to apoC-III, would decrease apoC-III, increase LPL activity, and lower triglycerides in PL., Methods: Five adults with PL enrolled in a 16-week placebo-controlled, randomized, double blind study of volanesorsen, 300 mg weekly, followed by 1-year open label extension., Results: Within-subject effects of volanesorsen before and after 16 weeks of active drug are reported due to small sample size. From week 0 to 16, apoC-III decreased from median (25 th , 75 th %ile) 380 (246, 600) to 75 (26, 232) ng/mL, and triglycerides decreased from 503 (330, 1040) to 116 (86, 355) mg/dL while activation of LPL by subjects' serum increased from 21 (20, 25) to 36 (29, 42) nEq/mL*min. Although, A1c did not change, peripheral and hepatic insulin sensitivity (glucose disposal and suppression of glucose production during hyperinsulinemic clamp) increased and palmitate turnover decreased. After 32-52 weeks of volanesorsen, liver fat decreased. Common adverse events included injection site reactions and decreased platelets., Conclusions: In PL, volanesorsen decreased apoC-III and triglycerides, in part through an LPL dependent mechanism, and may improve insulin resistance and hepatic steatosis., Competing Interests: Declaration of Competing Interest In-kind research support for this study (including study drug, analysis of pharmacokinetics and lipids, database management, patient remuneration and visiting nurse support) were provided by Ionis Pharmaceuticals and Akcea Therapeutics. All authors have declared that no conflict of interest exists., (Copyright © 2022. Published by Elsevier Inc.)

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 ε p1 and ε p2 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 ε p1 ground-truth median error of 0.009(0.007) vs. 0.32(0.385) using HARP and ε p2 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 ε p1 and ε p2 compared to R < 0.21 and R < 0.82 for HARP-generated maps, respectively., Conclusion: CNN-generated Eulerian strain mapping permits artifact-free visualization of myocardial function at the native image resolution., (Copyright © 2021. Published by Elsevier Ltd.)

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 of >50% 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 and Aims: Autosomal dominant hyper-IgE (AD-HIES) is a primary immunodeficiency caused by mutations in STAT3. Elevated levels of IgE, an ineffective immune response, connective tissue abnormalities, and coronary arterial dilation and tortuosity characterize AD-HIES. To date, coronary artery evaluation in AD-HIES patients has been limited to lumenography measurements. Direct in vivo coronary vessel wall (VW) imaging may allow for better interrogation of coronary vessel abnormalities. The goal of this prospective study was to evaluate the coronary VW of AD-HIES patients using Magnetic Resonance Imaging (MRI) and histology. VW image findings were compared in healthy subjects and subjects with coronary atherosclerotic disease (CAD)., Methods: A total of 28 subjects (10 with AD-HIES, 8 healthy, 10 with CAD) were studied by coronary VW MRI imaging. Additionally, a post-mortem coronary artery from one VW imaged AD-HIES patient was examined., Results: Coronary VW in AD-HIES was thicker than in healthy controls but not significantly different from VW thickness in CAD subjects. AD-HIES coronaries showed increased VW area compared to healthy controls and CAD subjects. On histology, the AD-HIES coronary artery had findings consistent with atherosclerotic plaque, but had minimal luminal narrowing, deficient adventitia thickening and absence of both internal and external elastic laminae., Conclusions: This is the first study to demonstrate subclinical coronary atherosclerosis in AD-HIES patients on VW imaging by MRI. Histologic evaluation confirmed the presence of atherosclerosis with lack of supportive adventitial thickening and elastic components. These findings suggest mechanisms for coronary dilation in AD-HIES and thereby help direct clinical management., (Published by Elsevier B.V.)

Objectives: 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., Materials and Methods: 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., Results: 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)., Conclusions: 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., (Published by Elsevier Inc.)

Unlabelled: Currently available infectious disease imaging techniques cannot differentiate between infection and sterile inflammation or between different types of infections. Recently, radiolabeled FIAU was found to be a substrate for the thymidine kinase (TK) enzyme of multiple pathogenic bacteria, leading to its translational use in the imaging of bacterial infections. Patients with immunodeficiencies, however, are susceptible to a different group of pathogenic bacteria when compared to immunocompetent subjects. In this study, we wanted to predict the usefulness of radiolabeled FIAU in the detection of bacterial infections commonly occurring in patients with immunodeficiencies, in vitro, prior to attempting in vivo imaging with (124)I-FIAU-PET., Methods: We obtained representative strains of bacterial pathogens isolated from actual patients with genetic immunodeficiencies. We evaluated the bacterial susceptibility of different strains to the effect of incubation with FIAU, which would implicate the presence of the thymidine kinase (TK) enzyme. We also incubated the bacteria with (14)C-FIAU and consequently measured its rate of incorporation in the bacterial DNA using a liquid scintillation counter., Results: Unlike the other bacterial strains, the growth of Pseudomonas aeruginosa was not halted by FIAU at any concentration. All the tested clinical isolates demonstrated different levels of (14)C-FIAU uptake, except for P. aeruginosa., Conclusion: Radiolabeled FIAU has been successful in delineating bacterial infections, both in preclinical and pilot translational studies. In patients with immunodeficiencies, Pseudomonas infections are commonly encountered and are usually difficult to differentiate from fungal infections. The use of radiolabeled FIAU for in vivo imaging of those patients, however, would not be useful, considering the apparent lack of TK enzyme in Pseudomonas. One has to keep in mind that not all pathogenic bacteria possess the TK enzyme and as such will not all retain FIAU. Our technique is simple, and can be easily used to assess whether a certain bacterial strain of interest can or cannot be visualized using radiolabeled FIAU., (Published by Elsevier Inc.)

Four different techniques for 3-T whole-heart coronary magnetic resonance angiography (MRA) using free-breathing three-dimensional segmented parallel imaging and adiabatic T2-preparation were assessed. Coronary MRA at 3 T is improved by shortening the acquisition window more than employing the highest spatial resolution. Double-oblique whole-heart acquisitions result in better overall image quality and allow for better delineation of the left anterior descending coronary artery. It is possible to attain shorter acquisition windows and a smaller voxel size at 3 T than previously reported at 1.5 T., (Published by Elsevier Inc.)

There are advantages to conducting cardiovascular magnetic resonance (CMR) studies at a field strength of 3.0 Telsa, including the increase in bulk magnetization, the increase in frequency separation of off-resonance spins, and the increase in T1 of many tissues. However, there are significant challenges to routinely performing CMR at 3.0 T, including the reduction in main magnetic field homogeneity, the increase in RF power deposition, and the increase in susceptibility-based artifacts.In this review, we outline the underlying physical effects that occur when imaging at higher fields, examine the practical results these effects have on the CMR applications, and examine methods used to compensate for these effects. Specifically, we will review cine imaging, MR coronary angiography, myocardial perfusion imaging, late gadolinium enhancement, and vascular wall imaging.