Viral airway injury promotes cell engraftment in an in vitro model of cystic fibrosis cell therapy.

Cell therapy is a potential treatment for cystic fibrosis (CF). However, cell engraftment into the airway epithelium is challenging. Here, we model cell engraftment in vitro using the air-liquid interface (ALI) culture system by injuring well-differentiated CF ALI cultures and delivering non-CF cells at the time of peak injury. Engraftment efficiency was quantified by measuring chimerism by droplet digital PCR and functional ion transport in Ussing chambers. Using this model, we found that human bronchial epithelial cells (HBECs) engraft more efficiently when they are cultured by conditionally reprogrammed cell (CRC) culture methods. Cell engraftment into the airway epithelium requires airway injury, but the extent of injury needed is unknown. We compared three injury models and determined that severe injury with partial epithelial denudation facilitates long-term cell engraftment and functional CFTR recovery up to 20% of wildtype function. The airway epithelium promptly regenerates in response to injury, creating competition for space and posing a barrier to effective engraftment. We examined competition dynamics by time-lapse confocal imaging and found that delivered cells accelerate airway regeneration by incorporating into the epithelium. Irradiating the repairing epithelium granted engrafting cells a competitive advantage by diminishing resident stem cell proliferation. Intentionally, causing severe injury to the lungs of people with CF would be dangerous. However, naturally occurring events like viral infection can induce similar epithelial damage with patches of denuded epithelium. We found that viral preconditioning promoted effective engraftment of cells primed for viral resistance.NEW & NOTEWORTHY Cell therapy is a potential treatment for cystic fibrosis (CF). Here, we model cell engraftment by injuring CF air-liquid interface cultures and delivering non-CF cells. Successful engraftment required severe epithelial injury. Intentionally injuring the lungs to this extent would be dangerous. However, naturally occurring events like viral infection induce similar epithelial damage. We found that viral preconditioning promoted the engraftment of cells primed for viral resistance leading to CFTR functional recovery to 20% of the wildtype.

A cleavable peptide adapter augments the activity of targeted toxins in combination with the glycosidic endosomal escape enhancer SO1861.

BACKGROUND: Treatment with tumor-targeted toxins attempts to overcome the disadvantages of conventional cancer therapies by directing a drug's cytotoxic effect specifically towards cancer cells. However, success with targeted toxins has been hampered as the constructs commonly remain bound to the outside of the cell or, after receptor-mediated endocytosis, are either transported back to the cell surface or undergo degradation in lysosomes. Hence, solutions to ensure endosomal escape are an urgent need in treatment with targeted toxins. In this work, a molecular adapter that consists of a cell penetrating peptide and two cleavable peptides was inserted into a targeted toxin between the ribosome-inactivating protein dianthin and the epidermal growth factor. Applying cell viability assays, this study examined whether the addition of the adapter further augments the endosomal escape enhancement of the glycosylated triterpenoid SO1861, which has shown up to more than 1000-fold enhancement in the past. RESULTS: Introducing the peptide adapter into the targeted toxin led to an about 12-fold enhancement in the cytotoxicity on target cells while SO1861 caused a 430-fold increase. However, the combination of adapter and glycosylated triterpenoid resulted in a more than 4300-fold enhancement and in addition to a 51-fold gain in specificity. CONCLUSIONS: Our results demonstrated that the cleavable peptide augments the endosomal escape mediated by glycosylated triterpenoids while maintaining specificity. Thus, the adapter is a promising addition to glycosylated triterpenoids to further increase the efficacy and therapeutic window of targeted toxins.

Unfolding coil localized errors from an imperfect slice profile using a structured autocalibration matrix: An application to reduce outflow effects in cine bSSFP imaging.

PURPOSE: Balanced steady-state free precession (bSSFP) imaging is susceptible to outflow effects where excited spins leaving the slice as part of the blood stream are misprojected back onto the imaging plane. Previous work proposed using slice-encoding steps to localize these outflow effects from corrupting the target slice, at the expense of prolonged scan time. This present study extends this idea by proposing a means of significantly reducing most of the outflowing signal from the imaged slice using a coil localization method that acquires a slice-encoded calibration scan in addition to the 2D data, without being nearly as time-demanding as our previous method. This coil localization method is titled UNfolding Coil Localized Errors from an imperfect slice profile using a Structured Autocalibration Matrix (UNCLE SAM). METHODS: Retrospective and prospective evaluations were carried out. Both featured a 2D acquisition and a separate slice-encoded calibration of the center in-plane k $$ k $$ -space lines across all desired slice-encoding steps. RESULTS: Retrospective results featured a slice-by-slice comparison of the slice-encoded images with UNCLE SAM. UNCLE SAM's subtraction from the slice-encoded image was compared with a subtraction from the flow-corrupted 2D image, to demonstrate UNCLE SAM's capability to unfold outflowing spins. UNCLE SAM's comparison with slice encoding showed that UNCLE SAM was able to unfold up to 74% of what slice encoding achieved. Prospective results showed significant reduction in outflow effects with only a marginal increase in scan time from the 2D acquisition. CONCLUSIONS: We developed a method that effectively unfolds most outflowing spins from corrupting the target slice and does not require the explicit use of slice-encoding gradients. This development offers a method to reduce most outflow effects from the target slice within a clinically feasible scan duration compared with the fully sampled slice-encoding technique.

ECG-free cine MRI with data-driven clustering of cardiac motion for quantification of ventricular function.

BACKGROUND: Despite the widespread use of cine MRI for evaluation of cardiac function, existing real-time methods do not easily enable quantification of ventricular function. Moreover, segmented cine MRI assumes periodicity of cardiac motion. We aim to develop a self-gated, cine MRI acquisition scheme with data-driven cluster-based binning of cardiac motion. METHODS: A Cartesian golden-step balanced steady-state free precession sequence with sorted k-space ordering was designed. Image data were acquired with breath-holding. Principal component analysis and k-means clustering were used for binning of cardiac phases. Cluster compactness in the time dimension was assessed using temporal variability, and dispersion in the spatial dimension was assessed using the Calinski-Harabasz index. The proposed and the reference electrocardiogram (ECG)-gated cine methods were compared using a four-point image quality score, SNR and CNR values, and Bland-Altman analyses of ventricular function. RESULTS: A total of 10 subjects with sinus rhythm and 8 subjects with arrhythmias underwent cardiac MRI at 3.0 T. The temporal variability was 45.6 ms (cluster) versus 24.6 ms (ECG-based) (p < 0.001), and the Calinski-Harabasz index was 59.1 ± 9.1 (cluster) versus 22.0 ± 7.1 (ECG based) (p < 0.001). In subjects with sinus rhythm, 100% of the end-systolic and end-diastolic images from both the cluster and reference approach received the highest image quality score of 4. Relative to the reference cine images, the cluster-based multiphase (cine) image quality consistently received a one-point lower score (p < 0.05), whereas the SNR and CNR values were not significantly different (p = 0.20). In cases with arrhythmias, 97.9% of the end-systolic and end-diastolic images from the cluster approach received an image quality score of 3 or more. The mean bias values for biventricular ejection fraction and volumes derived from the cluster approach versus reference cine were negligible. CONCLUSION: ECG-free cine cardiac MRI with data-driven clustering for binning of cardiac motion is feasible and enables quantification of cardiac function.

Dynamic Regularized Adaptive Cluster Optimization (DRACO) for Quantitative Cardiac Cine MRI in Complex Arrhythmias.

BACKGROUND: Irregular cardiac motion can render conventional segmented cine MRI nondiagnostic. Clustering has been proposed for cardiac motion binning and may be optimized for complex arrhythmias. PURPOSE: To develop an adaptive cluster optimization method for irregular cardiac motion, and to generate the corresponding time-resolved cine images. STUDY TYPE: Prospective. SUBJECTS: Thirteen with atrial fibrillation, four with premature ventricular contractions, and one patient in sinus rhythm. FIELD STRENGTH/SEQUENCE: Free-running balanced steady state free precession (bSSFP) with sorted golden-step, reference real-time sequence. ASSESSMENT: Each subject underwent both the sorted golden-step bSSFP and the reference Cartesian real-time imaging. Golden-step bSSFP images were reconstructed using the dynamic regularized adaptive cluster optimization (DRACO) method and k-means clustering. Image quality (4-point Likert scale), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), edge sharpness, and ventricular function were assessed. STATISTICAL TESTS: Paired t-tests, Friedman test, regression analysis, Fleiss' Kappa, Bland-Altman analysis. Significance level P < 0.05. RESULTS: The DRACO method had the highest percent of images with scores ≥3 (96% for diastolic frame, 93% for systolic frame, and 93% for multiphase cine) and the percentages were significantly higher compared with both the k-means and real-time methods. Image quality scores, SNR, and CNR were significantly different between DRACO vs. k-means and between DRACO vs. real-time. Cardiac function analysis showed no significant differences between DRACO vs. the reference real-time. CONCLUSION: DRACO with time-resolved reconstruction generated high quality images and has early promise for quantitative cine cardiac MRI in patients with complex arrhythmias including atrial fibrillation. TECHNICAL EFFICACY: Stage 2.

Ferumoxytol-Enhanced Cardiac Cine MRI Reconstruction Using a Variable-Splitting Spatiotemporal Network.

BACKGROUND: Balanced steady-state free precession (bSSFP) imaging is commonly used in cardiac cine MRI but prone to image artifacts. Ferumoxytol-enhanced (FE) gradient echo (GRE) has been proposed as an alternative. Utilizing the abundance of bSSFP images to develop a computationally efficient network that is applicable to FE GRE cine would benefit future network development. PURPOSE: To develop a variable-splitting spatiotemporal network (VSNet) for image reconstruction, trained on bSSFP cine images and applicable to FE GRE cine images. STUDY TYPE: Retrospective and prospective. SUBJECTS: 41 patients (26 female, 53 ± 19 y/o) for network training, 31 patients (19 female, 49 ± 17 y/o) and 5 healthy subjects (5 female, 30 ± 7 y/o) for testing. FIELD STRENGTH/SEQUENCE: 1.5T and 3T, bSSFP and GRE. ASSESSMENT: VSNet was compared to VSNet with total variation loss, compressed sensing and low rank methods for 14× accelerated data. The GRAPPA×2/×3 images served as the reference. Peak signal-to-noise-ratio (PSNR), structural similarity index (SSIM), left ventricular (LV) and right ventricular (RV) end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were measured. Qualitative image ranking and scoring were independently performed by three readers. Latent scores were calculated based on scores of each method relative to the reference. STATISTICS: Linear mixed-effects regression, Tukey method, Fleiss' Kappa, Bland-Altman analysis, and Bayesian categorical cumulative probit model. A P-value <0.05 was considered statistically significant. RESULTS: VSNet achieved significantly higher PSNR (32.7 ± 0.2), SSIM (0.880 ± 0.004), rank (2.14 ± 0.06), and latent scores (-1.72 ± 0.22) compared to other methods (rank >2.90, latent score < -2.63). Fleiss' Kappa was 0.52 for scoring and 0.61 for ranking. VSNet showed no significantly different LV and RV ESV (P = 0.938) and EF (P = 0.143) measurements, but statistically significant different (2.62 mL) EDV measurements compared to the reference. CONCLUSION: VSNet produced the highest image quality and the most accurate functional measurements for FE GRE cine images among the tested 14× accelerated reconstruction methods. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Regional variability of cardiovascular magnetic resonance access and utilization in the United States.

BACKGROUND: Clinical guidelines and scientific data increasingly support the appropriate use of cardiovascular magnetic resonance (CMR) . The extent of CMR adoption across the United States (US) remains unclear. This observational analysis aims to capture CMR practice patterns in the US. METHODS: Commissioned reports from the Society for Cardiovascular Magnetic Resonance (SCMR), pre-existing survey data from CMR centers, and socioeconomic and coronary heart disease data from the Centers for Disease Control and Prevention were used. The location of imaging centers performing CMR was based on 2018 Medicare claims. Secondary analysis was performed on center-specific survey data from 2017-2019, which were collected by members of the SCMR US Advocacy Subcommittee for quality improvement purposes. The correlation between the number of imaging centers billing for CMR services per million persons, socioeconomic determinants, and coronary heart disease epidemiology was determined. RESULTS: A total of 591 imaging centers billed the Center for Medicare & Medicaid Services for CMR services in 2018 and 112 (of 155) unique CMR centers responded to the survey. In 2018, CMR services were available in almost all 50 states. Minnesota was the state with the highest number of CMR centers per million Medicare beneficiaries (52.6 centers per million), and Maine had the lowest (4.4 per million). The total density of CMR centers was 16 per million for US Medicare beneficiaries. Sixty-eight percent (83 of 112) of survey responders were cardiologists, and 28% (31/112) were radiologists. In 72% (71/112) of centers, academic health care systems performed 81%-100% of CMR exams. The number of high-volume centers (>500 scans per year) increased by seven between 2017 and 2019. In 2019, 53% (59/112) of centers were considered high-volume centers and had an average of 19 years of experience. Centers performing <50 scans had on average 3.5 years of experience. Approximate patient wait time for a CMR exam was 2 weeks to 1 month. CONCLUSION: Despite increasing volume and availability in almost all 50 states, CMR access remains geographically variable. Advocacy efforts to improve access and innovations that reduce imaging time and exam complexity have the potential to increase the adoption of CMR technology.

Mid-term clinical and sonographic outcomes of minimally invasive acromioclavicular joint reconstruction: mini-open versus arthroscopically assisted.

INTRODUCTION: The current literature describes various operative stabilization strategies which achieve good clinical outcomes after acute acromioclavicular joint (ACJ) dislocation. The aim of this study was to compare the mid-term clinical and sonographic treatment outcomes after minimally invasive mini-open and arthroscopic reconstruction. MATERIALS AND METHODS: We conducted a retrospective two-center study of patients with acute ACJ dislocation. Surgical treatment was performed using either a mini-open approach (MIOP) or an arthroscopic technique (AR). The primary outcome parameters of this study were the sonographically measured acromioclavicular (ACD) and coracoclavicular distances (CCD). Secondary outcome parameters included the Constant-Murley score (CS), range of motion (ROM), postoperative pain scale (VAS), return to daily routine, return to sports, complications, as well as operative revisions. RESULTS: After a mean follow-up of 29 months, 30 patients were included in this study with an average age of 41.3 ± 14.8 years (MIOP) and 41.2 ± 15.4 years (AR). The sonographic ACD (MIOP 9.11 mm vs. AR 8.93 mm, p = 0.41) and CCD (MIOP 25.08 mm vs. AR 24.36 mm, p = 0.29) distances showed no statistically significant differences. Furthermore, there was no statistically significant difference when compared to the contralateral side (p = 0.42). With both techniques, patients achieved excellent clinical outcome parameters without statistically significant differences in CS (MIOP 95 vs. AR 97, p = 0.11) and VAS (MIOP 1.76 vs. AR 1.14, p = 0.18). The return to daily activity and return to sport rates did not differ. There were neither complications nor revisions in both groups. CONCLUSION: Both minimally invasive techniques for acute ACJ stabilization achieved excellent clinical and sonographic outcomes without one technique being statistically superior to the other.

Comparison of Three Ultrasmall, Superparamagnetic Iron Oxide Nanoparticles for MRI at 3.0 T.

BACKGROUND: The ultrasmall, superparamagnetic iron oxide (USPIO) nanoparticle ferumoxytol has unique applications in cardiac, vascular, and body magnetic resonance imaging (MRI) due to its long intravascular half-life and suitability as a blood pool agent. However, limited availability and high cost have hindered its clinical adoption. A new ferumoxytol generic, and the emergence of MoldayION as an alternative USPIO, represent opportunities to expand the use of USPIO-enhanced MRI techniques. PURPOSE: To compare in vitro and in vivo MRI relaxometry and enhancement of Feraheme, generic ferumoxytol, and MoldayION. STUDY TYPE: Prospective. ANIMAL MODEL: Ten healthy swine and six swine with artificially induced coronary narrowing underwent cardiac MRI. FIELD STRENGTH/SEQUENCE: 3.0 T; T1-weighted (4D-MUSIC, 3D-VIBE, 2D-MOLLI) and T2-weighted (2D-HASTE) sequences pre- and post-contrast. ASSESSMENT: We compared the MRI relaxometry of Feraheme, generic ferumoxytol, and MoldayION using saline, plasma, and whole blood MRI phantoms with contrast concentrations from 0.26 mM to 2.10 mM. In-vivo contrast effects on T1- and T2-weighted sequences and fractional intravascular contrast distribution volume in myocardium, liver, and spleen were evaluated. STATISTICAL TESTS: Analysis of variance and covariance were used for group comparisons. A P value <0.05 was considered statistically significant. RESULTS: The r1 relaxivities for Feraheme, generic ferumoxytol, and MoldayION in saline (22 °C) were 7.11 ± 0.13 mM-1  s-1 , 8.30 ± 0.29 mM-1  s-1 , 8.62 ± 0.16 mM-1  s-1 , and the r2 relaxivities were 111.74 ± 3.76 mM-1  s-1 , 105.07 ± 2.20 mM-1  s-1 , and 109.68 ± 2.56 mM-1  s-1 , respectively. The relationship between contrast concentration and longitudinal (R1) and transverse (R2) relaxation rate was highly linear in saline and plasma. The three agents produced similar in vivo contrast effects on T1 and T2 relaxation time-weighted sequences. DATA CONCLUSION: Relative to clinically approved ferumoxytol formulations, MoldayION demonstrates minor differences in in vitro relaxometry and comparable in vivo MRI characteristics. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Human airway lineages derived from pluripotent stem cells reveal the epithelial responses to SARS-CoV-2 infection.

There is an urgent need to understand how SARS-CoV-2 infects the airway epithelium and in a subset of individuals leads to severe illness or death. Induced pluripotent stem cells (iPSCs) provide a near limitless supply of human cells that can be differentiated into cell types of interest, including airway epithelium, for disease modeling. We present a human iPSC-derived airway epithelial platform, composed of the major airway epithelial cell types, that is permissive to SARS-CoV-2 infection. Subsets of iPSC-airway cells express the SARS-CoV-2 entry factors angiotensin-converting enzyme 2 (ACE2), and transmembrane protease serine 2 (TMPRSS2). Multiciliated cells are the primary initial target of SARS-CoV-2 infection. On infection with SARS-CoV-2, iPSC-airway cells generate robust interferon and inflammatory responses, and treatment with remdesivir or camostat mesylate causes a decrease in viral propagation and entry, respectively. In conclusion, iPSC-derived airway cells provide a physiologically relevant in vitro model system to interrogate the pathogenesis of, and develop treatment strategies for, COVID-19 pneumonia.

Automatic segmentation of peripheral arteries and veins in ferumoxytol-enhanced MR angiography.

PURPOSE: To automate the segmentation of the peripheral arteries and veins in the lower extremities based on ferumoxytol-enhanced MR angiography (FE-MRA). METHODS: Our automated pipeline has 2 sequential stages. In the first stage, we used a 3D U-Net with local attention gates, which was trained based on a combination of the Focal Tversky loss with region mutual loss under a deep supervision mechanism to segment the vasculature from the high-resolution FE-MRA datasets. In the second stage, we used time-resolved images to separate the arteries from the veins. Because the ultimate segmentation quality of the arteries and veins relies on the performance of the first stage, we thoroughly evaluated the different aspects of the segmentation network and compared its performance in blood vessel segmentation with currently accepted state-of-the-art networks, including Volumetric-Net, DeepVesselNet-FCN, and Uception. RESULTS: We achieved a competitive F1 = 0.8087 and recall = 0.8410 for blood vessel segmentation compared with F1 = (0.7604, 0.7573, 0.7651) and recall = (0.7791, 0.7570, 0.7774) obtained with Volumetric-Net, DeepVesselNet-FCN, and Uception. For the artery and vein separation stage, we achieved F1 = (0.8274/0.7863) in the calf region, which is the most challenging region in peripheral arteries and veins segmentation. CONCLUSION: Our pipeline is capable of fully automatic vessel segmentation based on FE-MRA without need for human interaction in <4 min. This method improves upon manual segmentation by radiologists, which routinely takes several hours.

Determination of the

We report the first measurement of the parity-violating elastic electron scattering asymmetry on ^{27}Al. The ^{27}Al elastic asymmetry is A_{PV}=2.16±0.11(stat)±0.16(syst) ppm, and was measured at ⟨Q^{2}⟩=0.02357±0.00010 GeV^{2}, ⟨θ_{lab}⟩=7.61°±0.02°, and ⟨E_{lab}⟩=1.157 GeV with the Q_{weak} apparatus at Jefferson Lab. Predictions using a simple Born approximation as well as more sophisticated distorted-wave calculations are in good agreement with this result. From this asymmetry the ^{27}Al neutron radius R_{n}=2.89±0.12 fm was determined using a many-models correlation technique. The corresponding neutron skin thickness R_{n}-R_{p}=-0.04±0.12 fm is small, as expected for a light nucleus with a neutron excess of only 1. This result thus serves as a successful benchmark for electroweak determinations of neutron radii on heavier nuclei. A tree-level approach was used to extract the ^{27}Al weak radius R_{w}=3.00±0.15 fm, and the weak skin thickness R_{wk}-R_{ch}=-0.04±0.15 fm. The weak form factor at this Q^{2} is F_{wk}=0.39±0.04.

MR Angiography Series: Noncardiac Chest MR Angiography.

This review guides readers through the selection and setup of standardized noncardiac chest MRA protocols, including contrast-enhanced MRA (CE-MRA) and noncontrast MRA (NC-MRA), sequences that can be used in a variety of clinical situations. After reviewing basic principles described in the first three tutorials in this series on CE-MRA and NC-MRA, this online presentation details the use of MRA in specific clinical scenarios: thoracic aortic aneurysm, aortic dissection, congenital heart disease, vasculitis, central veins, and pulmonary embolus. Tips and tricks for optimization of the sequences, image acquisition, and image interpretation are provided. This module is the fourth in a series created on behalf of the Society for Magnetic Resonance Angiography (SMRA), a group of researchers and clinicians who are passionate about the benefits of MRA but understand its challenges. The full digital presentation is available online. ©RSNA, 2022.

High-resolution three­dimensional contrast­enhanced magnetic resonance venography in children: comparison of gadofosveset trisodium with ferumoxytol.

BACKGROUND: Gadofosveset is a gadolinium-based blood pool contrast agent that was approved by the United States Food and Drug Administration in 2008. Its unanticipated withdrawal from production in 2016 created a void in the blood pool agent inventory and highlighted the need for an alternative agent with comparable imaging properties. OBJECTIVE: The purpose of our study is to compare the diagnostic image quality, vascular contrast-to-noise ratio (CNR) and temporal signal characteristics of gadofosveset trisodium and ferumoxytol at similar molar doses for high-resolution, three-dimensional (3-D) magnetic resonance (MR) venography in children. MATERIALS AND METHODS: The medical records and imaging data sets of patients who underwent high-resolution 3-D gadofosveset-enhanced MR venography (GE-MRV) or ferumoxytol-enhanced MR venography (FE-MRV) were retrospectively reviewed. Two groups of 20 pediatric patients (age- and weight-matched with one patient common to both groups; age range: 2 days-15 years) who underwent high-resolution 3-D GE-MRV or FE-MRV at similar molar doses were identified and analyzed. Qualitative analysis of image quality and vessel definition was performed by two blinded pediatric radiologists. Interobserver agreement was assessed with the AC1 (first-order agreement coefficient) statistic. Signal-to-noise ratio (SNR) and CNR of the inferior vena cava and aorta were measured in the steady-state venous phase. Medical records were retrospectively reviewed for any adverse reactions associated with either contrast agent. RESULTS: Measured SNR and CNR of the inferior vena cava were higher for FE-MRV than GE-MRV (P = 0.034 and P < 0.001, respectively). The overall image quality score and individual vessel scores of FE-MRV were equal to or greater than GE-MRV (P = 0.084), with good interobserver agreement (AC1 = 0.657). The venous signal on FE-MRV was stable over the longest interval measured (1 h, 13 min and 46 s), whereas venous signal on GE-MRV showed more variability and earlier loss of signal. No adverse reactions were noted in any patient with either contrast agent. CONCLUSION: Ferumoxytol produces more uniform and stable enhancement throughout the entire venous circulation in children than gadofosveset, offering a wider time window for optimal image acquisition. FE-MRV offers a near-ideal approach to high-resolution venography in children at all levels of anatomical complexity.

Four-dimensional Multiphase Steady-State MRI with Ferumoxytol Enhancement: Early Multicenter Feasibility in Pediatric Congenital Heart Disease.

Background The value of MRI in pediatric congenital heart disease (CHD) is well recognized; however, the requirement for expert oversight impedes its widespread use. Four-dimensional (4D) multiphase steady-state imaging with contrast enhancement (MUSIC) is a cardiovascular MRI technique that uses ferumoxytol and captures all anatomic features dynamically. Purpose To evaluate multicenter feasibility of 4D MUSIC MRI in pediatric CHD. Materials and Methods In this prospective study, participants with CHD underwent 4D MUSIC MRI at 3.0 T or 1.5 T between 2014 and 2020. From a pool of 460 total studies, an equal number of MRI studies from three sites (n = 60) was chosen for detailed analysis. With use of a five-point scale, the feasibility of 4D MUSIC was scored on the basis of artifacts, image quality, and diagnostic confidence for intracardiac and vascular connections (n = 780). Respiratory motion suppression was assessed by using the signal intensity profile. Bias between 4D MUSIC and two-dimensional (2D) cine imaging was evaluated by using Bland-Altman analysis; 4D MUSIC examination duration was compared with that of the local standard for CHD. Results A total of 206 participants with CHD underwent MRI at 3.0 T, and 254 participants underwent MRI at 1.5 T. Of the 60 MRI examinations chosen for analysis (20 per site; median participant age, 14.4 months [interquartile range, 2.3-49 months]; 33 female participants), 56 (93%) had good or excellent image quality scores across a spectrum of disease complexity (mean score ± standard deviation: 4.3 ± 0.6 for site 1, 4.9 ± 0.3 for site 2, and 4.6 ± 0.7 for site 3; P < .001). Artifact scores were inversely related to image quality (r = -0.88, P < .001) and respiratory motion suppression (P < .001, r = -0.45). Diagnostic confidence was high or definite in 730 of 780 (94%) intracardiac and vascular connections. The correlation between 4D MUSIC and 2D cine ventricular volumes and ejection fraction was high (range of r = 0.72-0.85; P < .001 for all). Compared with local standard MRI, 4D MUSIC reduced the image acquisition time (44 minutes ± 20 vs 12 minutes ± 3, respectively; P < .001). Conclusion Four-dimensional multiphase steady-state imaging with contrast enhancement MRI in pediatric congenital heart disease was feasible in a multicenter setting, shortened the examination time, and simplified the acquisition protocol, independently of disease complexity. Clinical trial registration no. NCT02752191 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Roest and Lamb in this issue.

Slice encoding for the reduction of outflow signal artifacts in cine balanced SSFP imaging.

PURPOSE: Standard balanced SSFP (bSSFP) cine MRI often suffers from blood outflow artifacts. We propose a method that spatially encodes these outflowing spins to reduce their effects in the intended slice. METHODS: Bloch simulations were performed to characterize through-plane flow and to investigate how the use of phase encoding along the slice select's direction ("slice encoding") could alleviate its issues. Phantom scans and in vivo cines were acquired on a 3T system, comparing the standard 2D acquisition to the proposed slice-encoding method. Nineteen healthy volunteers were recruited for short-axis and horizontal long-axis oriented scans. An expert radiologist evaluated each slice-encoded/standard cine pairs in a rank comparison test and graded their quality on a 1-5 scale. The grades were used for a nonparametric paired evaluation for independent samples with a null hypothesis that there was no statistical difference between the two quality-grade distributions for α = 0.05 significance. RESULTS: Bloch simulation results demonstrated this technique's feasibility, showing a fully resolved slice profile given a sufficient number of slice encodes. These results were confirmed with the phantom experiments. Each in vivo slice-encoded cine had a higher quality than its corresponding standard acquisition. The nonparametric paired evaluation came to 0.01 significance, encouraging us to reject the null hypothesis and conclude that slice-encoding effectively works in reducing outflow effects. CONCLUSION: The slice-encoding balanced SSFP technique is helpful in mitigating outflow effects and is achievable within a single breath hold, being a useful alternative for cases in which the flow artifacts are significant.

Temporally aware volumetric generative adversarial network-based MR image reconstruction with simultaneous respiratory motion compensation: Initial feasibility in 3D dynamic cine cardiac MRI.

PURPOSE: Develop a novel three-dimensional (3D) generative adversarial network (GAN)-based technique for simultaneous image reconstruction and respiratory motion compensation of 4D MRI. Our goal was to enable high-acceleration factors 10.7X-15.8X, while maintaining robust and diagnostic image quality superior to state-of-the-art self-gating (SG) compressed sensing wavelet (CS-WV) reconstruction at lower acceleration factors 3.5X-7.9X. METHODS: Our GAN was trained based on pixel-wise content loss functions, adversarial loss function, and a novel data-driven temporal aware loss function to maintain anatomical accuracy and temporal coherence. Besides image reconstruction, our network also performs respiratory motion compensation for free-breathing scans. A novel progressive growing-based strategy was adapted to make the training process possible for the proposed GAN-based structure. The proposed method was developed and thoroughly evaluated qualitatively and quantitatively based on 3D cardiac cine data from 42 patients. RESULTS: Our proposed method achieved significantly better scores in general image quality and image artifacts at 10.7X-15.8X acceleration than the SG CS-WV approach at 3.5X-7.9X acceleration (4.53 ± 0.540 vs. 3.13 ± 0.681 for general image quality, 4.12 ± 0.429 vs. 2.97 ± 0.434 for image artifacts, P < .05 for both). No spurious anatomical structures were observed in our images. The proposed method enabled similar cardiac-function quantification as conventional SG CS-WV. The proposed method achieved faster central processing unit-based image reconstruction (6 s/cardiac phase) than the SG CS-WV (312 s/cardiac phase). CONCLUSION: The proposed method showed promising potential for high-resolution (1 mm3 ) free-breathing 4D MR data acquisition with simultaneous respiratory motion compensation and fast reconstruction time.

Alkyne Aminopalladation/Heck and Suzuki Cascades: An Approach to Tetrasubstituted Enamines.

Alkyne aminopalladation reactions starting from tosylamides are reported. The emerging vinylic Pd species are converted either in an intramolecular Heck reaction with olefinic units or in an intermolecular Suzuki reaction by using boronic acids exhibiting broad functional group tolerance. Tetra(hetero)substituted tosylated enamines are obtained in a simple one-pot process.

Estimation of fractional myocardial blood volume and water exchange using ferumoxytol-enhanced magnetic resonance imaging.

Fractional myocardial blood volume (fMBV) estimated using ferumoxytol-enhanced magnetic resonance imaging (MRI) (FE-MRI) has the potential to capture a hemodynamic response to myocardial hypoperfusion during contrast steady state without reliance on gadolinium chelates. Ferumoxytol has a long intravascular half-life and its use for steady-state MRI is off-label. The aim of this prospective study was to optimize and evaluate a two-compartment model for estimation of fMBV based on FE-MRI. Nine healthy swine and one swine with artificially induced single-vessel coronary stenosis underwent MRI on a 3.0 T clinical magnet. Myocardial longitudinal spin-lattice relaxation rate (R1) was measured using the 5(3)3(3)3 modified Look-Locker inversion recovery (MOLLI) sequence before and at contrast steady state following seven ferumoxytol infusions (0.125-4.0 mg/kg). fMBV and water exchange were estimated using a two-compartment model. Model-fitted fMBV was compared to simple fast-exchange fMBV approximation and percent change in pre- and postferumoxytol R1. Dose undersampling schemes were investigated to reduce acquisition duration. Variation in fMBV was assessed using one-way analysis of variance. Fast-exchange fMBV and ferumoxytol dose undersampling were evaluated using Bland-Altman analysis. Healthy normal swine showed a mean mid-ventricular fMBV of 7.2 ± 1.4% and water exchange rate of 11.3 ± 5.1 s-1 . There was intersubject variation in fMBV (p < 0.05) without segmental variation (p = 0.387). fMBV derived from eight-dose and four-dose sampling schemes had no significant bias (mean difference = 0.07, p = 0.541, limits of agreement -1.04% [-1.45, -0.62%] to 1.18% [0.77, 1.59%]). Pixel-wise fMBV in one swine model with coronary artery stenosis showed elevated fMBV in ischemic segments (apical anterior: 11.90 ± 4.00%, apical septum: 16.10 ± 5.71%) relative to remote segments (apical inferior: 9.59 ± 3.35%, apical lateral: 9.38 ± 2.35%). A two-compartment model based on FE-MRI using the MOLLI sequence may enable estimation of fMBV in studies of ischemic heart disease. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

A landscape classification map of Ireland and its potential use in national land use monitoring.

This study presents a novel landscape classification map of the Republic of Ireland and is the first to identify broad landscape classes by incorporating physiographic and land cover data. The landscape classification responds to commitments to identify and classify the Irish landscape as a signatory to the European Landscape Convention. The methodology applied a series of clustering iterations to determine an objective multivariate classification of physiographic landscape units and land cover datasets. The classification results determined nine statistically significant landscape classes and the development of a landscape classification map at a national scale. A statistical breakdown of land cover area and diversity of each class was interpreted, and a comparison was extended using independent descriptive variables including farmland use intensity, elevation, and dominant soil type. Each class depicts unique spatial and composition characteristics, from coastal, lowland and elevated, to distinct and dominating land cover types, further explained by the descriptive variables. The significance of individual classes and success of the classification is discussed with particular reference to the wider applicability of the map. The transferability of the methodology to other existing physiographic maps and environmental datasets to generate new landscape classifications is also considered. This novel work facilitates the development of a strategic framework to efficiently monitor, compare and analyse ecological and other land use data that is spatially representative of the distribution and extent of land cover in the Irish countryside.