Flow evaluation software for four-dimensional flow MRI: a reliability and validation study.

PURPOSE: Four-dimensional time-resolved phase-contrast cardiovascular magnetic resonance imaging (4D flow MRI) enables blood flow quantification in multiple vessels, which is crucial for patients with congenital heart disease (CHD). We investigated net flow volumes in the ascending aorta and pulmonary arteries by four different postprocessing software packages for 4D flow MRI in comparison with 2D cine phase-contrast measurements (2D PC). MATERIAL AND METHODS: 4D flow and 2D PC datasets of 47 patients with biventricular CHD (median age 16, range 0.6-52 years) were acquired at 1.5 T. Net flow volumes in the ascending aorta, the main, right, and left pulmonary arteries were measured using four different postprocessing software applications and compared to offset-corrected 2D PC data. Reliability of 4D flow postprocessing software was assessed by Bland-Altman analysis and intraclass correlation coefficient (ICC). Linear regression of internal flow controls was calculated. Interobserver reproducibility was evaluated in 25 patients. RESULTS: Correlation and agreement of flow volumes were very good for all software compared to 2D PC (ICC ≥ 0.94; bias ≤ 5%). Internal controls were excellent for 2D PC (r ≥ 0.95, p < 0.001) and 4D flow (r ≥ 0.94, p < 0.001) without significant difference of correlation coefficients between methods. Interobserver reliability was good for all vendors (ICC ≥ 0.94, agreement bias < 8%). CONCLUSION: Haemodynamic information from 4D flow in the large thoracic arteries assessed by four commercially available postprocessing applications matches routinely performed 2D PC values. Therefore, we consider 4D flow MRI-derived data ready for clinical use in patients with CHD.

Feasibility of Non-Gated Dynamic Fetal Cardiac MRI for Identification of Fetal Cardiovascular Anatomy.

INTRODUCTION: The aim of this study was to evaluate the feasibility of identifying the fetal cardiac and thoracic vascular structures with non-gated dynamic balanced steady-state free precession (SSFP) MRI sequences. METHODS: We retrospectively assessed the visibility of cardiovascular anatomy in 60 fetuses without suspicion of congenital heart defect. Non-gated dynamic balanced SSFP sequences were acquired in three anatomic planes of the fetal thorax. The images were analyzed following a segmental approach in consensus reading by an experienced pediatric cardiologist and radiologist. An imaging score was defined by giving one point to each visualized structure, yielding a maximum score of 21 points. Image quality was rated from 0 (poor) to 2 (excellent). The influence of gestational age (GA), field strength, placenta position, and maternal panniculus on image quality and imaging score were tested. RESULTS: 30 scans were performed at 1.5T, 30 at 3T. Heart position, atria, and ventricles could be seen in all 60 fetuses. Basic diagnosis (>12 points) was achieved in 54 cases. The mean imaging score was 16.8+/-3.8. Maternal panniculus (r = -0.3; p = 0.015) and GA (r = 0.6; p < 0.001) correlated with imaging score. Field strength influenced image quality, with 1.5T being better than 3T images (p = 0.012). Imaging score or quality was independent of placenta position. CONCLUSION: Fetal cardiac MRI with non-gated SSFP sequences enables recognition of basic cardiovascular anatomy.

Signal Thresholding Segmentation of Ventricular Volumes in Young Patients with Various Diseases-Can We Trust the Numbers?

In many cardiac diseases, right and left ventricular volumes in systole and diastole are diagnostically and prognostically relevant. Measurements are made by segmentation of the myocardial borders on cardiac magnetic resonance (CMR) images. Automatic detection of myocardial contours is possible by signal thresholding techniques, but must be validated before use in clinical settings. Biventricular volumes were measured in end-diastole (EDVi) and in end-systole (ESVi) both manually and with the MassK application, with signal thresholds at 30%, 50%, and 70%. Stroke volumes (SV) and cardiac indices (CI) were calculated from volumetric measurements and from flow measured in the ascending aorta and the main pulmonary artery, and both methods were compared. Reproducibility of volumetric measurements was tested in 20 patients. Measurements were acquired in 94 patients aged 15 ± 9 years referred for various conditions. EDVi and ESVi of both ventricles were largest with manual segmentation and inversely proportional to the MassK threshold. Manual and k30 SV and CI corresponded best to flow measurements. Interobserver variability was low for all volumes manually and with MassK. In conclusion, manual and 30% threshold-based biventricular volume segmentation agree best with two-dimensional, phantom-corrected phase contrast flow measurements in a young cardiac referral population and are well reproducible.

Possible effects of left pulmonary artery stenting in single ventricle patients on bronchial area, lung volume and lung function.

Background: Left pulmonary artery (LPA) stenting is often required in single ventricle (SV) patients. Due to their close anatomical relationship an LPA stent could potentially compress the left main bronchus (LMB). We assessed the impact of LPA stenting on bronchial size, pulmonary volumes, and lung function in a cohort of SV patients. Methods: Forty-nine patients underwent cardiovascular magnetic resonance (CMR) and 36 spirometry 11 (8-15) years after Fontan. All patients were free of respiratory symptoms. LPA stents were inserted in 17 (35%) patients at 8.8 (3.4-12.6) years. Area/shape of the main bronchi (n = 46) and lung volumes (n = 47) were calculated from CMR-ZTE images for each lung and transformed in right-to-left (r/l) ratio and indexed for BSA. The effect of early stent insertion (prior to stage III) was analyzed. Results: Patients with LPA stent had larger r/l ratio for main bronchus area (p < 0.001) and r/l ratio difference for lung volumes was slightly larger in patients with early stenting. A trend toward a deformation of LMB shape in patients with LPA stent and toward a higher prevalence of abnormal spirometry in patients with early stent implantation was observed. Conclusions: In this cohort of patients, early insertion of LPA stents seems to relate with smaller LMB sizes and a trend toward smaller left lung volume and higher prevalence of impaired lung function. Whether these findings are caused by the stent or, at least to a certain degree, present prior to the implantation needs to be verified.

Safety, Pharmacokinetics, and Pharmacodynamics of CC-90001 (BMS-986360), a c-Jun N-terminal Kinase Inhibitor, in Phase 1 Studies in Healthy Participants.

CC-90001 selectively inhibits c-Jun N-terminal kinase (JNK), a stress-activated protein implicated in fibrosis. In 3 phase 1 trials evaluating CC-90001 pharmacokinetics, pharmacodynamics, and safety, healthy adults (N = 184) received oral CC-90001 in a single dose (10-720 mg) or multiple doses (30-480 mg once daily for 7-18 days) or placebo. CC-90001 was rapidly absorbed (median time to maximum concentration, 1-4 hours) and eliminated with a mean terminal elimination half-life of 12-28 hours. Steady state was reached on day 5, with a mean accumulation ratio of 1.5- to 2-fold following daily dosing. Exposure was similar in fed versus fasted participants and in Japanese versus non-Japanese participants. CC-90001 demonstrated dose- and exposure-dependent inhibition of JNK as determined by histopathological analysis of c-Jun phosphorylation in ultraviolet-irradiated skin. The most common treatment-emergent adverse events were nausea and headache; all were mild or moderate in intensity. Based on exposure-response analysis using high-quality electrocardiogram data, no clinically relevant QT prolongation liability for CC-90001 was observed. Overall, single- and multiple-dose CC-90001 were generally safe and well tolerated at the tested doses and demonstrated JNK pathway engagement. These results support further clinical evaluation of CC-90001.

Quantitative evaluation of aortic valve regurgitation in 4D flow cardiac magnetic resonance: at which level should we measure?

PURPOSE: To find the best level to measure aortic flow for quantification of aortic regurgitation (AR) in 4D flow CMR. METHODS: In 27 congenital heart disease patients with AR (67% male, 31 ± 16 years) two blinded observers measured antegrade, retrograde, net aortic flow volumes and regurgitant fractions at 6 levels in 4D flow: (1) below the aortic valve (AV), (2) at the AV, (3) at the aortic sinus, (4) at the sinotubular junction, (5) at the level of the pulmonary arteries (PA) and (6) below the brachiocephalic trunk. 2D phase contrast (2DPC) sequences were acquired at the level of PA. All patients received prior transthoracic echocardiography (TTE) with AR severity grading according to a recommended multiparametric approach. RESULTS: After assigning 2DPC measurements into AR grading, agreement between TTE AR grading and 2DPC was good (κ = 0.88). In 4D flow, antegrade flow was similar between the six levels (p = 0.87). Net flow was higher at level 1-2 than at levels 3-6 (p < 0.05). Retrograde flow and regurgitant fraction at level 1-2 were lower compared to levels 3-6 (p < 0.05). Reproducibility (inter-reader agreement: ICC 0.993, 95% CI 0.986-0.99; intra-reader agreement: ICC 0.982, 95%CI 0.943-0.994) as well as measurement agreement between 4D flow and 2DPC (ICC 0.994; 95%CI 0.989 - 0.998) was best at the level of PA. CONCLUSION: For estimating severity of AR in 4D flow, best reproducibility along with best agreement with 2DPC measurements can be expected at the level of PA. Measurements at AV or below AV might underestimate AR.

Physical Activity in Fontan Patients Relates to Quality of Life and Sleep Quality.

Background and Aim: Fontan patients tend to have reduced physical exercise capacity. This study investigates physical activity (PA) and its relationship to exercise capacity, heart rates, cardiac function, biomarkers, health-related quality of life (HRQoL), and sleep quality. Methods: Cardiovascular magnetic resonance (CMR), exercise testing (CPET), 24 h-ECG, and blood samples were prospectively performed in 38 patients, age 13 (11-16) years. PA was assessed by accelerometer during 7 consecutive days. HRQoL was self-assessed with KIDSCREEN-27 and SF-36 according to patients' age; sleep quality with Pediatric Sleep Questionnaire (PSQ) and Pittsburgh Sleep Quality Index (PSQI). Results: Daily moderate to vigorous physical activity (MVPA) was in median (IQR) 40 (28-57) mins; 7/38 (18%) patients reached the recommended 60 mins/day of MVPA. MVPA did not correlate with gender, age, single ventricle morphology, time from Fontan, heart rate, ventricular volumes, and ejection fraction at CMR, biomarkers, or CPET. Physical wellbeing (r = 0.33, p = 0.04), autonomy (r = 0.39, p = 0.03), and social support (r = 0.43, p = 0.009) assessed using the KIDSCREEN-27, and both physical (r = 0.57, p = 0.03) and mental (r = 0.54, p = 0.04) domains of the SF-36 questionnaire correlated with daily minutes of MVPA. PSQI global sleeping score (r = -0.7, p = 0.007), and PSQ scales for behavior (r = -0.36; p = 0.03) correlated with daily minutes of MVPA. Conclusion: Only 18% of the Fontan patients meet the recommendation for daily MVPA. Measures of exercise capacity, cardiac function or chronotropic competence are not correlated to daily physical activity. In contrast, HRQoL and sleep quality seem to be associated with regular physical activity.

Advanced Imaging and New Cardiac Biomarkers in Long-term Follow-up After Childhood Cancer.

OBJECTIVES: Pathologic ejection fraction (EF), shortening fraction (FS), and standard heart failure biomarkers (high sensitive troponin T and N-terminal brain natriuretic peptide) during follow-up after childhood cancer have been associated with irreversible cardiac damage. We aimed to evaluate strain imaging values by echocardiography and new biomarkers for heart failure with preserved ejection fraction (HFpEF) as potential more sensitive parameters for cardiac deterioration in childhood cancer survivors (CCS). MATERIALS AND METHODS: Prospective study with 50 CCS (median 16.2 y) at a median follow-up of 13 years. In addition to standard echo and laboratory parameters for heart failure, strain measurements and new biomarkers, including myocardial inflammation (interleukin 6), extracellular matrix (ECM) remodeling (C-telopeptide for type I collagen, intact N-terminal propeptide of type III procollagen), and other heart failure biomarkers (galectin 3, solutable ST2, growth differentiation factor 15), were obtained and compared with 50 healthy controls. RESULTS: No significant differences in EF, FS, high sensitive troponin T, N-terminal brain natriuretic peptide, interleukin 6, solutable ST2, and galectin 3 were found between study and control groups. In contrast, strain imaging showed significant differences between both groups (global longitudinal strainGLS -16.1% vs. -20.4%, P<0.0001; global circumferential strain -14.3 vs. -21.4%, P<0.0001), detecting 66% (global longitudinal strain) and 76% (global circumferential strain) of patients with pathologic values in contrast to 6% (EF) and 16% (FS) for standard parameters. Markers for disturbances of ECM remodeling (C-telopeptide for type I collagen, intact N-terminal propeptide of type III procollagen, each P<0.0001) and growth differentiation factor 15 (P<0.0001) were significantly different between the groups. CONCLUSION: Strain imaging and new cardiac biomarkers used in HFpEF focusing on ECM remodeling appear to be more sensitive in detecting early remodeling processes in CCS than standard echo and laboratory parameters.

Myocardial Deformation in Fontan Patients Assessed by Cardiac Magnetic Resonance Feature Tracking: Correlation with Function, Clinical Course, and Biomarkers.

Cardiac MR (CMR) is a standard modality for assessing ventricular function of single ventricles. CMR feature-tracking (CMR-FT) is a novel application enabling strain measurement on cine MR images and is used in patients with congenital heart diseases. We sought to assess the feasibility of CMR-FT in Fontan patients and analyze the correlation between CMR-FT strain values and conventional CMR volumetric parameters, clinical findings, and biomarkers. Global circumferential (GCS) and longitudinal (GLS) strain were retrospectively measured by CMR-FT on Steady-State Free Precession cine images. Data regarding post-operative course at Fontan operation, and medication, exercise capacity, invasive hemodynamics, and blood biomarkers at a time interval ± 6 months from CMR were collected. Forty-seven patients underwent CMR 11 ± 6 years after the Fontan operation; age at CMR was 15 ± 7 years. End-diastolic volume (EDV) of the SV was 93 ± 37 ml/m2, end-systolic volume (ESV) was 46 ± 23 ml/m2, and ejection fraction (EF) was 51 ± 11%. Twenty (42%) patients had a single right ventricle (SRV). In single left ventricle (SLV), GCS was higher (p < 0.001), but GLS was lower (p = 0.04) than in SRV. GCS correlated positively with EDV (p = 0.005), ESV (p < 0.001), and EF (p ≤ 0.0001). GLS correlated positively with EF (p = 0.002), but not with ventricular volumes. Impaired GCS correlated with decreased ventricular function (p = 0.03) and atrioventricular valve regurgitation (p = 0.04) at echocardiography, direct atriopulmonary connection (p = 0.02), post-operative complications (p = 0.05), and presence of a rudimentary ventricle (p = 0.01). A reduced GCS was associated with increased NT-pro-BNP (p = 0.05). Myocardial deformation can be measured by CMR-FT in Fontan patients. SLVs have higher GCS, but lower GLS than SRVs. GCS correlates with ventricular volumes and EF, whereas GLS correlates with EF only. Myocardial deformation shows a relationship with several clinical parameters and NT-pro-BNP.

Left Ventricular Torsion Obtained Using Equilibrated Warping in Patients with Repaired Tetralogy of Fallot.

Patients after surgical repair of Tetralogy of Fallot (rTOF) may suffer a decrease in left ventricular (LV) function. The aim of our study is to evaluate a novel method of assessing LV torsion in patients with rTOF, as an early indicator of systolic LV dysfunction. Motion tracking based on image registration regularized by the equilibrium gap principle, known as equilibrated warping, was employed to assess LV torsion. Seventy-six cases of rTOF and ten normal controls were included. The group of controls was assessed for reproducibility using both equilibrated warping and standard clinical tissue tracking software (CVI42, version 5.10.1, Calgary, Canada). Patients were dichotomized into two groups: normal vs. loss of torsion. Torsion by equilibrated warping was successfully obtained in 68 of 76 (89%) patients and 9 of 10 (90%) controls. For equilibrated warping, the intra- and interobserver coefficients of variation were 0.095 and 0.117, respectively, compared to 0.260 and 0.831 for tissue tracking by standard clinical software. The intra- and inter-observer intraclass correlation coefficients for equilibrated warping were 0.862 and 0.831, respectively, compared to 0.992 and 0.648 for tissue tracking. Loss of torsion was noted in 32 of the 68 (47%) patients with rTOF. There was no difference in LV or RV volumes or ejection fraction between these groups. The assessment of LV torsion by equilibrated warping is feasible and shows good reliability. Loss of torsion is common in patients with rTOF and its robust assessment might contribute into uncovering heart failure in an earlier stage.

Assessment of ventricular flow dynamics by 4D-flow MRI in patients following surgical repair of d-transposition of the great arteries.

OBJECTIVES: To use 4D-flow MRI to describe systemic and non-systemic ventricular flow organisation and energy loss in patients with repaired d-transposition of the great arteries (d-TGA) and normal subjects. METHODS: Pathline tracking of ventricular volumes was performed using 4D-flow MRI data from a 1.5-T GE Discovery MR450 scanner. D-TGA patients following arterial switch (n = 17, mean age 14 ± 5 years) and atrial switch (n = 15, 35 ± 6 years) procedures were examined and compared with subjects with normal cardiac anatomy and ventricular function (n = 12, 12 ± 3 years). Pathlines were classified by their passage through the ventricles as direct flow, retained inflow, delayed ejection flow, and residual volume and visually and quantitatively assessed. Additionally, viscous energy losses (ELv) were calculated. RESULTS: In normal subjects, the ventricular flow paths were well ordered following similar trajectories through the ventricles with very little mixing of flow components. The flow paths in all atrial and some arterial switch patients were more irregular with high mixing. Direct flow and delayed ejection flow were decreased in atrial switch patients' systemic ventricles with a corresponding increase in residual volume compared with normal subjects (p = 0.003 and p < 0.001 respectively) and arterial switch patients (p < 0.0001 and p < 0.001 respectively). In non-systemic ventricles, arterial switch patients had increased direct flow and decreased delayed ejection fractions compared to normal (p = 0.007 and p < 0.001 respectively) and atrial switch patients (p = 0.01 and p < 0.001 respectively). Regions of high levels of mixing of ventricular flow components showed elevated ELv. CONCLUSIONS: 4D-flow MRI pathline tracking reveals disordered ventricular flow patterns and associated ELv in d-TGA patients. KEY POINTS: • 4D-flow MRI can be used to assess intraventricular flow dynamics in d-TGA patients. • d-TGA arterial switch patients mostly show intraventricular flow dynamics representative of normal subjects, while atrial switch patients show increased flow disorder and different proportions of intraventricular flow volumes. • Flow disruption and disorder increase viscous energy losses.

Retraining Convolutional Neural Networks for Specialized Cardiovascular Imaging Tasks: Lessons from Tetralogy of Fallot.

Ventricular contouring of cardiac magnetic resonance imaging is the gold standard for volumetric analysis for repaired tetralogy of Fallot (rTOF), but can be time-consuming and subject to variability. A convolutional neural network (CNN) ventricular contouring algorithm was developed to generate contours for mostly structural normal hearts. We aimed to improve this algorithm for use in rTOF and propose a more comprehensive method of evaluating algorithm performance. We evaluated the performance of a ventricular contouring CNN, that was trained on mostly structurally normal hearts, on rTOF patients. We then created an updated CNN by adding rTOF training cases and evaluated the new algorithm's performance generating contours for both the left and right ventricles (LV and RV) on new testing data. Algorithm performance was evaluated with spatial metrics (Dice Similarity Coefficient (DSC), Hausdorff distance, and average Hausdorff distance) and volumetric comparisons (e.g., differences in RV volumes). The original Mostly Structurally Normal (MSN) algorithm was better at contouring the LV than the RV in patients with rTOF. After retraining the algorithm, the new MSN + rTOF algorithm showed improvements for LV epicardial and RV endocardial contours on testing data to which it was naïve (N = 30; e.g., DSC 0.883 vs. 0.905 for LV epicardium at end diastole, p < 0.0001) and improvements in RV end-diastolic volumetrics (median %error 8.1 vs 11.4, p = 0.0022). Even with a small number of cases, CNN-based contouring for rTOF can be improved. This work should be extended to other forms of congenital heart disease with more extreme structural abnormalities. Aspects of this work have already been implemented in clinical practice, representing rapid clinical translation. The combined use of both spatial and volumetric comparisons yielded insights into algorithm errors.

Additional value and new insights by four-dimensional flow magnetic resonance imaging in congenital heart disease: application in neonates and young children.

Cardiovascular MRI has become an essential imaging modality in children with congenital heart disease (CHD) in the last 15-20 years. With use of appropriate sequences, it provides important information on cardiovascular anatomy, blood flow and function for initial diagnosis and post-surgical or -interventional monitoring in children. Although considered as more sophisticated and challenging than CT, in particular in neonates and infants, MRI is able to provide information on intra- and extracardiac haemodynamics, in contrast to CT. In recent years, four-dimensional (4-D) flow MRI has emerged as an additional MR technique for retrospective assessment and visualisation of blood flow within the heart and any vessel of interest within the acquired three-dimensional (3-D) volume. Its application in young children requires special adaptations for the smaller vessel size and faster heart rate compared to adolescents or adults. In this article, we provide an overview of 4-D flow MRI in various types of complex CHD in neonates and infants to demonstrate its potential indications and beneficial application for optimised individual cardiovascular assessment. We focus on its application in clinical routine cardiovascular workup and, in addition, show some examples with pathologies other than CHD to highlight that 4-D flow MRI yields new insights in disease understanding and therapy planning. We shortly review the essentials of 4-D flow data acquisition, pre- and post-processing techniques in neonates, infants and young children. Finally, we conclude with some details on accuracy, limitations and pitfalls of the technique.

Real-World Experience Measurement of Liver Iron Concentration by R2 vs. R2 Star MRI in Hemoglobinopathies.

BACKGROUND: Non-invasive determination of liver iron concentration (LIC) is a valuable tool that guides iron chelation therapy in transfusion-dependent patients. Multiple methods have been utilized to measure LIC by MRI. The purpose of this study was to compare free breathing R2* (1/T2*) to whole-liver Ferriscan R2 method for estimation of LIC in a pediatric and young adult population who predominantly have hemoglobinopathies. METHODS: Clinical liver and cardiac MRI scans from April 2016 to May 2018 on a Phillips 1.5 T scanner were reviewed. Free breathing T2 and T2* weighted images were acquired on each patient. For T2, multi-slice spin echo sequences were obtained. For T2*, a single mid-liver slice fast gradient echo was performed starting at 0.6 ms with 1.2 ms increments with signal averaging. R2 measurements were performed by Ferriscan analysis. R2* measurements were performed by quantitative T2* map analysis. RESULTS: 107 patients underwent liver scans with the following diagnoses: 76 sickle cell anemia, 20 Thalassemia, 9 malignancies and 2 Blackfan Diamond anemia. Mean age was 12.5 ± 4.5 years. Average scan time for R2 sequences was 10 min, while R2* sequence time was 20 s. R2* estimation of LIC correlated closely with R2 with a correlation coefficient of 0.94. Agreement was strongest for LIC < 15 mg Fe/g dry weight. Overall bias from Bland-Altman plot was 0.66 with a standard deviation of 2.8 and 95% limits of agreement -4.8 to 6.1. CONCLUSION: LIC estimation by R2* correlates well with R2-Ferriscan in the pediatric age group. Due to the very short scan time of R2*, it allows imaging without sedation or anesthesia. Cardiac involvement was uncommon in this cohort.

Normal myocardial native T1 values in children using single-point saturation recovery and modified look-locker inversion recovery (MOLLI).

BACKGROUND: T1 mapping is useful to quantify diffuse myocardial processes such as fibrosis, edema, storage disorders, or hemochromatosis. Normal pediatric myocardial T1 values are scarce using modified Look-Locker inversion recovery (MOLLI) sequences and unavailable using Smart1Map, a single-point saturation recovery sequence that measures true T1 . PURPOSE/HYPOTHESIS: To establish normal pediatric myocardial T1 values by Smart1Map and to compare them with T1 by MOLLI. STUDY TYPE: Prospective cohort study. SUBJECTS: Thirty-four children and adolescents aged 8-18 years (14 males) without cardiovascular or inflammatory diseases. FIELD STRENGTH/SEQUENCES: 1.5T, MOLLI, Smart1Map. ASSESSMENT: Mean T1 values of the left ventricular myocardium, the interventricular septum, and the blood pool were measured with MOLLI and Smart1Map in basal, mid-ventricular, and apical short axis slices. STATISTICAL TESTS: T1 values were compared between locations and methods by paired samples t-tests, Wilcoxon signed ranks test, repeated-measures analysis of variance (ANOVA), or Friedman's test. Pearson's correlation coefficient was calculated. For interobserver variability, intraclass correlation coefficients and coefficients of variation were calculated, and Bland-Altman analyses were performed. RESULTS: T1 values were longer by Smart1Map than by MOLLI in all measured locations (myocardium: 1191-1221 vs. 990-1042 msec; all P < 0.001). T1 in basal vs. mid-ventricular slices differed both by MOLLI and by Smart1Map for myocardium and for blood (all P < 0.001). Myocardial T1 did not correlate with age, heart rate, right or left ventricular ejection fraction (all P > 0.05) by either method. Septal vs. total myocardial T1 values in each slice did not differ by MOLLI (basal P = 0.371; mid-ventricular P = 0.08; apical P = 0.378) nor by Smart1Map (basal P = 0.056; mid-ventricular P = 0.918; apical P = 0. 392), after artifacts had been carefully excluded. DATA CONCLUSION: We established pediatric normal native T1 values using the Smart1Map sequence and compared the results with T1 mapping with MOLLI. Septal T1 values did not differ from total myocardial T1 values in each of the myocardial slices. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:897-903.

Flow quantification dependency on background phase correction techniques in 4D-flow MRI.

PURPOSE: To analyze the dependence of flow volume measurements on 3D cine phase-contrast MRI (4D-flow MRI) background phase correction. METHODS: In 31 subjects scanned on a 1.5T MRI scanner, flow volume measurements at 4 vessels were made using phantom corrected 2D phase contrast and 4D flow with background phase correction performed by linear, second, third, and fourth-order polynomial fitting to static tissue. Variations in the amount and distribution of static tissue were made to investigate the influence on flow volume measurements. RESULTS: Bland Altman comparison of 2D phase-contrast and 4D-flow measurements showed low bias (2.3%-4.8%) and relatively large limits of agreement (13.5%-17.6%). Approximately half of this was attributable to sequence and physiological differences between the 2 scan sequences, demonstrated by smaller limits of agreement (5.3%-10.0%) when comparing 4D-flow measurements with differing background phase corrections. Using only 20% of available static tissue points for polynomial fitting resulted in only 1% difference in flow volume measurements. Using asymmetrically distributed static tissue or including nonstatic tissue for polynomial fitting yielded highly variable differences in flow volume measurements, which became more variable with increased polynomial order. Completely asymmetric static tissue selection resulted in high deviations in flow volume measurements (mean > 7%, max = 345%). CONCLUSION: Comparisons between 2D phase-contrast and 4D-flow volume measurements should consider influences from sequence and physiological differences. A subset of static tissue points may be used with low impact on flow measurements, but should avoid the inclusion of nonstatic tissue and avoid asymmetric distribution. Higher-order polynomial fits are more susceptible to inaccurate static tissue selection.

Ductus arteriosus-associated infective endarteritis: Lessons from the past, future perspective.

BACKGROUND: Since routine clinical use of antibiotics as well as surgical and catheter-based closure of a patent arterial duct (PDA), PDA-associated infective endarteritis (PDA-IE) is rare but can still occur when the ductus is still open or as it closes. Thus, clinicians should maintain a high index of concern for patients with unexplained fever. METHODS: We report on a PDA-IE in a young infant shortly after potentially delayed obliteration of a PDA. We discuss this case report by reviewing the literature in regard to the pathogenesis (infection primary or secondary to PDA thrombus formation), clinical (new heart murmur) and diagnostic findings (transthoracic echocardiography, total body MRI, laboratory findings), and clinical outcome during mid-term follow-up after successful antibiotic treatment. RESULTS: A 7-week-old term infant with Staphylococcus aureus sepsis and a new heart murmur was diagnosed with PDA-IE by transthoracic echocardiography at the pulmonary artery end of an obliterated PDA. Broad diagnostic workup excluded other reasons for sepsis. After 4 weeks of antibiotic treatment the vegetation reduced in size and the infant recovered completely. A review of all cases of PDA-IE (in pediatric and adult patients) previously published was performed. CONCLUSION: Nowadays, a PDA-IE is an extremely rare, but still life-threating condition that may even affect patients with a nonpatent ductus arteriosus shortly after its obliteration and should be considered as infective complication in preterms, neonates, and small infants. Therefore, in septic neonates with bacteremia, transthoracic echocardiography may be integrated in the diagnostic workup, especially by fever without source and clinical signs of IE such as a new heart murmur.

Creating three dimensional models of the right ventricular outflow tract: influence of contrast, sequence, operator, and threshold.

The use of 3D printed models of the right ventricular outflow tract (RVOT) for surgical and interventional planning is growing and often requires image segmentation of cardiac magnetic resonance (CMR) images. Segmentation results may vary based on contrast, image sequence, signal threshold chosen by the operator, and manual post-processing. The purpose of this study was to determine potential biases and post-processing errors in image segmentation to enable informed decisions. Models of the RVOT and pulmonary arteries from twelve patients who had contrast enhanced CMR angiography with gadopentetate dimeglumine (GPD), gadofosveset trisodium (GFT), and a post-GFT inversion-recovery (IR) whole heart sequence were segmented, trimmed, and aligned by three operators. Geometric agreement and minimal RVOT diameters were compared between sequences and operators. To determine the contribution of threshold, interoperator variability was compared between models created by the same two operators using the same versus different thresholds. Geometric agreement by Dice between objects was high (intraoperator: 0.89-0.95; interoperator: 0.95-0.97), without differences between sequences. Minimal RVOT diameters differed on average by - 1.9 to - 1.3 mm (intraoperator) and by 0.4 to 1.4 mm (interoperator). The contribution of threshold to interoperator geometric agreement was not significant (same threshold: 0.96 ± 0.06, different threshold: 0.93 ± 0.05; p = 0.181), but minimal RVOT diameters were more variable with different versus constant thresholds (- 9.12% vs. 2.42%; p < 0.05). Thresholding does not significantly change interoperator variability for geometric agreement, but does for minimal RVOT diameter. Minimal RVOT diameters showed clinically relevant variation within and between operators.

Pediatric heterozygous familial hypercholesterolemia patients have locally increased aortic pulse wave velocity and wall thickness at the aortic root.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder that affects 1 in 250 people. Aortic stiffness, measured by pulse wave velocity (PWV), is an independent predictor for cardiovascular events. Young FH patients are a unique group with early vessel wall disease that may serve to elucidate the determinants of aortic stiffness. We hypothesized that young FH patients would have early changes in aortic stiffness compared to healthy, age- and sex-matched reference values. Thirty-three FH patients ( ≥ 7 years age; mean age 14.6 ± 3.3 years; 26/33 on statin therapy) underwent cardiac MRI. PWV was determined using propagation of flow waveform from aortic arch phase contrast images. Distensibility and aortic wall thickness (AWT) were measured at the ascending, proximal descending, and diaphragmatic aorta. Ventricular volumes and left ventricular (LV) myocardial mass were measured from 2D cine images. These parameters were compared to age- and sex-matched reference values. FH patients had significantly higher PWV (4.5 ± 0.8 vs. 3.5 ± 0.3 m/s; p < 0.001), aortic distensibility, and ascending aortic wall thickness (1.37 ± 0.18 vs. 1.30 ± 0.02 mm; p < 0.05) compared to reference. There was no difference in aortic area or descending aortic wall thickness between groups. Young FH patients had aortic changes with increased aortic pulse wave velocity in the setting of increased aortic distensibility, accompanied by increased thickness of the ascending aortic wall. Presence of these early findings in young patients despite the majority being on statin therapy support enhanced screening and aggressive treatment of familial hypercholesterolemia to prevent potential future cardiovascular events.