Comprehensive left atrial flow component analysis reveals abnormal flow patterns in paroxysmal atrial fibrillation.

Left atrial (LA) blood flow plays an important role in diseases such as atrial fibrillation (AF) and atrial cardiomyopathy since alterations in the blood flow might lead to thrombus formation and stroke. Using traditional techniques, such as echocardiography, atrial flow velocities can be measured at the pulmonary veins and the mitral valve, but a comprehensive understanding of the three-dimensional atrial flow field is missing. Previously, ventricular flow has been analyzed using flow component analysis, revealing new insights into ventricular flow and function. Thus, the aim of this project was to develop a comprehensive flow component analysis method for the LA and explore its utility in 21 patients with paroxysmal atrial fibrillation compared with a control group of 8 participants. The flow field was derived from time-resolved CT acquired during sinus rhythm using computational fluid dynamics. Flow components were computed from particle tracking. We identified six atrial flow components: conduit, reservoir, delayed ejection, retained inflow, residual volume, and pulmonary vein backflow. It was shown that conduit flow, defined as blood entering and leaving the LA within the same diastolic phase, exists in most subjects. Although the volume of conduit and reservoir is similar in patients with paroxysmal AF in sinus rhythm and controls, the volume of the other components is increased in paroxysmal AF. Comprehensive quantification of LA flow using flow component analysis makes atrial blood flow quantifiable, thus facilitating investigation of mechanisms underlying atrial dysfunction and can increase understanding of atrial blood flow in disease progression and stroke risk.NEW & NOTEWORTHY We developed a new comprehensive approach to atrial blood component analysis that includes both conduit flow and residual volume and compared the flow components of atrial fibrillation (AF) patients in sinus rhythm with controls. Conduit and reservoir flow were similar between the groups, whereas components with longer residence time in the left atrium were increased in the AF group. This could add to the pathophysiological understanding of atrial diseases and possibly clinical management.

Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women.

BACKGROUND: Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population. METHODS: Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50-64 years. Breathlessness (modified Medical Research Council [mMRC] ≥ 2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease. RESULTS: We included 25,948 people aged 57.5 ± [SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0-29.9), 21% obese (BMI ≥ 30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6-66.0%), stress (31.6-76.8%), respiratory disease (20.1-37.1%), depression (17.1-26.6%), cardiac disease (6.3-12.7%), anemia (0.8-3.3%), and peripheral arterial disease (0.3-0.8%). Stress was the main factor in women and current smokers. CONCLUSION: Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting-supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.

Liver fibrosis is associated with left ventricular remodeling: insight into the liver-heart axis.

OBJECTIVE: In nonalcoholic fatty liver disease (NAFLD), liver fibrosis is the strongest predictor of adverse outcomes. We sought to investigate the relationship between liver fibrosis and cardiac remodeling in participants from the general population using magnetic resonance imaging (MRI), as well as explore potential mechanistic pathways by analyzing circulating cardiovascular biomarkers. METHODS: In this cross-sectional study, we prospectively included participants with type 2 diabetes and individually matched controls from the SCAPIS (Swedish CArdioPulmonary bioImage Study) cohort in Linköping, Sweden. Between November 2017 and July 2018, participants underwent MRI at 1.5 Tesla for quantification of liver proton density fat fraction (spectroscopy), liver fibrosis (stiffness from elastography), left ventricular (LV) structure and function, as well as myocardial native T1 mapping. We analyzed 278 circulating cardiovascular biomarkers using a Bayesian statistical approach. RESULTS: In total, 92 participants were enrolled (mean age 59.5 ± 4.6 years, 32 women). The mean liver stiffness was 2.1 ± 0.4 kPa. 53 participants displayed hepatic steatosis. LV concentricity increased across quartiles of liver stiffness. Neither liver fat nor liver stiffness displayed any relationships to myocardial tissue characteristics (native T1). In a regression analysis, liver stiffness was related to increased LV concentricity. This association was independent of diabetes and liver fat (Beta = 0.26, p = 0.0053), but was attenuated (Beta = 0.17, p = 0.077) when also adjusting for circulating levels of interleukin-1 receptor type 2. CONCLUSION: MRI reveals that liver fibrosis is associated to structural LV remodeling, in terms of increased concentricity, in participants from the general population. This relationship could involve the interleukin-1 signaling. CLINICAL RELEVANCE STATEMENT: Liver fibrosis may be considered a cardiovascular risk factor in patients without cirrhosis. Further research on the mechanisms that link liver fibrosis to left ventricular concentricity may reveal potential therapeutic targets in patients with non-alcoholic fatty liver disease (NAFLD). KEY POINTS: Previously, studies on liver fibrosis and cardiac remodeling have focused on advanced stages of liver fibrosis. Liver fibrosis is associated with left ventricular (LV) concentricity and may relate to interleukin-1 receptor type 2. Interleukin-1 signaling is a potential mechanistic interlink between early liver fibrosis and LV remodeling.

Haemodynamic effects of hypertension and type 2 diabetes: Insights from a 4D flow MRI-based personalized cardiovascular mathematical model.

Type 2 diabetes (T2D) and hypertension increase the risk of cardiovascular diseases mediated by whole-body changes to metabolism, cardiovascular structure and haemodynamics. The haemodynamic changes related to hypertension and T2D are complex and subject-specific, however, and not fully understood. We aimed to investigate the haemodynamic mechanisms in T2D and hypertension by comparing the haemodynamics between healthy controls and subjects with T2D, hypertension, or both. For all subjects, we combined 4D flow magnetic resonance imaging data, brachial blood pressure and a cardiovascular mathematical model to create a comprehensive subject-specific analysis of central haemodynamics. When comparing the subject-specific haemodynamic parameters between the four groups, the predominant haemodynamic difference is impaired left ventricular relaxation in subjects with both T2D and hypertension compared to subjects with only T2D, only hypertension and controls. The impaired relaxation indicates that, in this cohort, the long-term changes in haemodynamic load of co-existing T2D and hypertension cause diastolic dysfunction demonstrable at rest, whereas either disease on its own does not. However, through subject-specific predictions of impaired relaxation, we show that altered relaxation alone is not enough to explain the subject-specific and group-related differences; instead, a combination of parameters is affected in T2D and hypertension. These results confirm previous studies that reported more adverse effects from the combination of T2D and hypertension compared to either disease on its own. Furthermore, this shows the potential of personalized cardiovascular models in providing haemodynamic mechanistic insights and subject-specific predictions that could aid in the understanding and treatment planning of patients with T2D and hypertension. KEY POINTS: The combination of 4D flow magnetic resonance imaging data and a cardiovascular mathematical model allows for a comprehensive analysis of subject-specific haemodynamic parameters that otherwise cannot be derived non-invasively. Using this combination, we show that diastolic dysfunction in subjects with both type 2 diabetes (T2D) and hypertension is the main group-level difference between controls, subjects with T2D, subjects with hypertension, and subjects with both T2D and hypertension. These results suggest that, in this relatively healthy population, the additional load of both hypertension and T2D affects the haemodynamic function of the left ventricle, whereas each disease on its own is not enough to cause significant effects under resting conditions. Finally, using the subject-specific model, we show that the haemodynamic effects of diastolic dysfunction alone are not sufficient to explain all the observed haemodynamic differences. Instead, additional subject-specific variations in cardiac and vascular function combine to explain the complex haemodynamics of subjects affected by hypertension and/or T2D.

Automatic Time-Resolved Cardiovascular Segmentation of 4D Flow MRI Using Deep Learning.

BACKGROUND: Segmenting the whole heart over the cardiac cycle in 4D flow MRI is a challenging and time-consuming process, as there is considerable motion and limited contrast between blood and tissue. PURPOSE: To develop and evaluate a deep learning-based segmentation method to automatically segment the cardiac chambers and great thoracic vessels from 4D flow MRI. STUDY TYPE: Retrospective. SUBJECTS: A total of 205 subjects, including 40 healthy volunteers and 165 patients with a variety of cardiac disorders were included. Data were randomly divided into training (n = 144), validation (n = 20), and testing (n = 41) sets. FIELD STRENGTH/SEQUENCE: A 3 T/time-resolved velocity encoded 3D gradient echo sequence (4D flow MRI). ASSESSMENT: A 3D neural network based on the U-net architecture was trained to segment the four cardiac chambers, aorta, and pulmonary artery. The segmentations generated were compared to manually corrected atlas-based segmentations. End-diastolic (ED) and end-systolic (ES) volumes of the four cardiac chambers were calculated for both segmentations. STATISTICAL TESTS: Dice score, Hausdorff distance, average surface distance, sensitivity, precision, and miss rate were used to measure segmentation accuracy. Bland-Altman analysis was used to evaluate agreement between volumetric parameters. RESULTS: The following evaluation metrics were computed: mean Dice score (0.908 ± 0.023) (mean ± SD), Hausdorff distance (1.253 ± 0.293 mm), average surface distance (0.466 ± 0.136 mm), sensitivity (0.907 ± 0.032), precision (0.913 ± 0.028), and miss rate (0.093 ± 0.032). Bland-Altman analyses showed good agreement between volumetric parameters for all chambers. Limits of agreement as percentage of mean chamber volume (LoA%), left ventricular: 9.3%, 13.5%, left atrial: 12.4%, 16.9%, right ventricular: 9.9%, 15.6%, and right atrial: 18.7%, 14.4%; for ED and ES, respectively. DATA CONCLUSION: The addition of this technique to the 4D flow MRI assessment pipeline could expedite and improve the utility of this type of acquisition in the clinical setting. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 1.

Enhancing students' understanding of cardiac physiology by using 4D visualization.

Difficulties in achieving knowledge about physiology and anatomy of the beating heart highlight the challenges with more traditional pedagogical methods. Recent research regarding anatomy education has mainly focused on digital three-dimensional models. However, these pedagogical improvements may not be entirely applicable to cardiac anatomy and physiology due to the multidimensional complexity with moving anatomy and complex blood flow. The aim of this study was therefore to evaluate whether high quality time-resolved anatomical images combined with realistic blood flow simulations improve the understanding of cardiac structures and function. Three time-resolved datasets were acquired using time-resolved computed tomography and blood flow was computed using Computational Fluid Dynamics. The anatomical and blood flow information was combined and interactively visualized using volume rendering on an advanced stereo projection system. The setup was tested in interactive lectures for medical students. Ninety-seven students participated. Summative assessment of examinations showed significantly improved mean score (18.1 ± 4.5 vs 20.3 ± 4.9, p = 0.002). This improvement was driven by knowledge regarding myocardial hypertrophy and pressure-velocity differences over a stenotic valve. Additionally, a supplementary formative assessment showed significantly more agreeing answers than disagreeing answers (p < 0.001) when the participants subjectively evaluated the contribution of the visualizations to their education and knowledge. In conclusion, the use of simultaneous visualization of time-resolved anatomy data and simulated blood flow improved medical students' results, with a particular effect on understanding of cardiac physiology and these simulations may be useful educational tools for teaching complex anatomical and physiological concepts.

Simultaneous Assessment of Left Atrial Fibrosis and Epicardial Adipose Tissue Using 3D Late Gadolinium Enhanced Dixon MRI.

BACKGROUND: Epicardial adipose tissue (EAT) may induce left atrium (LA) wall inflammation and promote LA fibrosis. Therefore, simultaneous assessment of these two important atrial fibrillation (AF) risk factors would be desirable. PURPOSE: To perform a comprehensive evaluation of 3D Dixon water-fat separated late gadolinium enhancement (LGE-Dixon) MRI by analysis of repeatability and systematic comparison with reference methods for assessment of fibrosis and fat. STUDY TYPE: Prospective. POPULATION: Twenty-eight, 10, and 7 patients, respectively, with clinical indications for cardiac MRI. FIELD STRENGTH/SEQUENCE: A 1.5-T scanner, inversion recovery multiecho spoiled gradient echo. ASSESSMENT: Twenty-eight patients (age 58 ± 19 years, 15 males) were scanned using LGE-Dixon. A 5-point Likert-type scale was used to grade the image quality. Another 10 patients (age 46 ± 19 years, 9 males) were scanned using LGE-Dixon and 3D proton density Dixon (PD-Dixon). Finally, seven patients (age 62 ± 14 years, 4 males) were scanned using LGE-Dixon and conventional LGE. The scan time, intraobserver and interobserver variability, and levels of agreement were assessed. STATISTICAL TESTS: Student's t-test, one-way ANOVA, and Mann-Whitney U-test were used; P < 0.05 was considered significant, intraclass correlation coefficient (ICC). RESULTS: The scan time (minutes:seconds) for LGE-Dixon (n = 28) was 5:01 ± 1:40. ICC values for intraobserver and interobserver measurements of LA wall fibrosis percentage were 0.98 (95% CI, 0.97-0.99) and 0.97 (95% CI, 0.94-0.99) while of EAT were 0.92 (95% CI, 0.82-0.97) and 0.90 (95% CI, 0.80-0.95). The agreement for LA fibrosis percentage between the LGE-Dixon and the conventional LGE was 0.92 (95% CI, 0.66-0.99) and for EAT volume between the LGE-Dixon and the PD-Dixon was 0.93 (95% CI, 0.72-0.98). CONCLUSION: LA fibrosis and EAT can be assessed simultaneously using LGE-Dixon. This method allows a high level of intraobserver and interobserver repeatability as well as agreement with reference methods and can be performed in a clinically feasible scan time. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 3.

Non-contrast myocardial perfusion in rest and exercise stress using systolic flow-sensitive alternating inversion recovery.

OBJECTIVE: To evaluate systolic flow-sensitive alternating inversion recovery (FAIR) during rest and exercise stress using 2RR (two cardiac cycles) or 1RR intervals between inversion pulse and imaging. MATERIALS AND METHODS: 1RR and 2RR FAIR was implemented on a 3T scanner. Ten healthy subjects were scanned during rest and stress. Stress was performed using an in-bore ergometer. Heart rate, mean myocardial blood flow (MBF) and temporal signal-to-noise ratio (TSNR) were compared using paired t tests. RESULTS: Mean heart rate during stress was higher than rest for 1RR FAIR (85.8 ± 13.7 bpm vs 63.3 ± 11.1 bpm; p < 0.01) and 2RR FAIR (83.8 ± 14.2 bpm vs 63.1 ± 10.6 bpm; p < 0.01). Mean stress MBF was higher than rest for 1RR FAIR (2.97 ± 0.76 ml/g/min vs 1.43 ± 0.6 ml/g/min; p < 0.01) and 2RR FAIR (2.8 ± 0.96 ml/g/min vs 1.22 ± 0.59 ml/g/min; p < 0.01). Resting mean MBF was higher for 1RR FAIR than 2RR FAIR (p < 0.05), but not during stress. TSNR was lower for stress compared to rest for 1RR FAIR (4.52 ± 2.54 vs 10.12 ± 3.69; p < 0.01) and 2RR FAIR (7.36 ± 3.78 vs 12.41 ± 5.12; p < 0.01). 2RR FAIR TSNR was higher than 1RR FAIR for rest (p < 0.05) and stress (p < 0.001). DISCUSSION: We have demonstrated feasibility of systolic FAIR in rest and exercise stress. 2RR delay systolic FAIR enables non-contrast perfusion assessment during stress with relatively high TSNR.

Myocardial arterial spin labeling in systole and diastole using flow-sensitive alternating inversion recovery with parallel imaging and compressed sensing.

Quantitative myocardial perfusion can be achieved without contrast agents using flow-sensitive alternating inversion recovery (FAIR) arterial spin labeling. However, FAIR has an intrinsically low sensitivity, which may be improved by mitigating the effects of physiological noise or by increasing the area of artifact-free myocardium. The aim of this study was to investigate if systolic FAIR may increase the amount of analyzable myocardium compared with diastolic FAIR and its effect on physiological noise. Furthermore, we compare parallel imaging acceleration with a factor of 2 with compressed sensing acceleration with a factor of 3 for systolic FAIR. Twelve healthy subjects were scanned during rest on a 3 T scanner using diastolic FAIR with parallel imaging factor 2 (FAIR-PI2D ), systolic FAIR with the same acceleration (FAIR-PI2S ) and systolic FAIR with compressed sensing factor 3 (FAIR-CS3S ). The number of analyzable pixels in the myocardium, temporal signal-to-noise ratio (TSNR) and mean myocardial blood flow (MBF) were calculated for all methods. The number of analyzable pixels using FAIR-CS3S (663 ± 55) and FAIR-PI2S (671 ± 58) was significantly higher than for FAIR-PI2D (507 ± 82; P = .001 for both), while there was no significant difference between FAIR-PI2S and FAIR-CS3S . The mean TSNR of the midventricular slice for FAIR-PI2D was 11.4 ± 3.9, similar to that of FAIR-CS3S, which was 11.0 ± 3.3, both considerably higher than for FAIR-PI2S, which was 8.4 ± 3.1 (P < .05 for both). Mean MBF was similar for all three methods. The use of compressed sensing accelerated systolic FAIR benefits from an increased number of analyzable myocardial pixels compared with diastolic FAIR without suffering from a TSNR penalty, unlike systolic FAIR with parallel imaging acceleration.

Using Deep Learning to Emulate the Use of an External Contrast Agent in Cardiovascular 4D Flow MRI.

BACKGROUND: Although contrast agents would be beneficial, they are seldom used in four-dimensional (4D) flow magnetic resonance imaging (MRI) due to potential side effects and contraindications. PURPOSE: To develop and evaluate a deep learning architecture to generate high blood-tissue contrast in noncontrast 4D flow MRI by emulating the use of an external contrast agent. STUDY TYPE: Retrospective. SUBJECTS: Of 222 data sets, 141 were used for neural network (NN) training (69 with and 72 without contrast agent). Evaluation was performed on the remaining 81 noncontrast data sets. FIELD STRENGTH/SEQUENCES: Gradient echo or echo-planar 4D flow MRI at 1.5 T and 3 T. ASSESSMENT: A cyclic generative adversarial NN was trained to perform image translation between noncontrast and contrast data. Evaluation was performed quantitatively using contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), structural similarity index (SSIM), mean squared error (MSE) of edges, and Dice coefficient of segmentations. Three observers performed a qualitative assessment of blood-tissue contrast, noise, presence of artifacts, and image structure visualization. STATISTICAL TESTS: The Wilcoxon rank-sum test evaluated statistical significance. Kendall's concordance coefficient assessed interobserver agreement. RESULTS: Contrast in the regions of interest (ROIs) in the NN enhanced images increased by 88%, CNR increased by 63%, and SNR improved by 48% (all P < 0.001). The SSIM was 0.82 ± 0.01, and the MSE of edges was 0.09 ± 0.01 (range [0,1]). Segmentations based on the generated images resulted in a Dice similarity increase of 15.25%. The observers managed to differentiate between contrast MR images and our results; however, they preferred the NN enhanced images in 76.7% of cases. This percentage increased to 93.3% for phase-contrast MR angiograms created from the NN enhanced data. Visual grading scores were blood-tissue contrast = 4.30 ± 0.74, noise = 3.12 ± 0.98, and presence of artifacts = 3.63 ± 0.76. Image structures within and without the ROIs resulted in scores of 3.42 ± 0.59 and 3.07 ± 0.71, respectively (P < 0.001). DATA CONCLUSION: The proposed approach improves blood-tissue contrast in MR images and could be used to improve data quality, visualization, and postprocessing of cardiovascular 4D flow data. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Evaluating the prevalence and severity of NAFLD in primary care: the EPSONIP study protocol.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects 20-30% of the general adult population. NAFLD patients with type 2 diabetes mellitus (T2DM) are at an increased risk of advanced fibrosis, which puts them at risk of cardiovascular complications, hepatocellular carcinoma, or liver failure. Liver biopsy is the gold standard for assessing hepatic fibrosis. However, its utility is inherently limited. Consequently, the prevalence and characteristics of T2DM patients with advanced fibrosis are unknown. Therefore, the purpose of the current study is to evaluate the prevalence and severity of NAFLD in patients with T2DM by recruiting participants from primary care, using the latest imaging modalities, to collect a cohort of well phenotyped patients. METHODS: We will prospectively recruit 400 patients with T2DM using biomarkers to assess their status. Specifically, we will evaluate liver fat content using magnetic resonance imaging (MRI); hepatic fibrosis using MR elastography and vibration-controlled transient elastography; muscle composition and body fat distribution using water-fat separated whole body MRI; and cardiac function, structure, and tissue characteristics, using cardiovascular MRI. DISCUSSION: We expect that the study will uncover potential mechanisms of advanced hepatic fibrosis in NAFLD and T2DM and equip the clinician with better diagnostic tools for the care of T2DM patients with NAFLD. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT03864510. Registered 6 March 2019, https://clinicaltrials.gov/ct2/show/NCT03864510 .

Inflow artifact reduction using an adaptive flip-angle navigator restore pulse for late gadolinium enhancement of the left atrium.

PURPOSE: Late gadolinium enhancement (LGE) of the left atrium is susceptible to artifacts arising from the right pulmonary veins, caused by inflowing blood tagged by the navigator restore pulse. The purpose of this study was to evaluate a new method to reduce the inflow artifact using an adaptive flip-angle restore pulse. METHODS: A low-restore angle reduces the inflow artifact but may lead to a poor navigator SNR. The proposed approach aims to determine the patient-specific restore angle, which optimizes the trade-off between inflow artifacts and navigator SNR. Three-dimensional LGE with adaptive navigator restore (3D LGEA ) was implemented by incrementing the flip angle of the restore pulse from a starting value of 0°, based on the navigator normalized cross-correlation. Magnetic resonance imaging experiments were performed on a 1.5T scanner. The value of 3D LGEA was compared with 3D LGE with a constant 180° restore pulse (3D LGE180 ) in 22 patients with heart diseases. The values of 3D LGEA and 3D LGE180 were compared in terms of pulmonary vein blood signal relative to reference blood in the descending aorta (PVrel ) and visual scoring to determine level of motion artifacts using a 4-point scale (1 = severe artifacts; 4 = no artifacts). RESULTS: The value of PVrel was significantly lower for 3D LGEA than for 3D LGE180 (1.16 ± 0.23 vs. 1.59 ± 0.29, P < .001). Furthermore, visual scoring of the motion artifacts yielded no difference (P = .78). CONCLUSION: Adaptively adjusting the navigator restore flip angle based on the navigator normalized cross-correlation reduces the 3D LGE inflow artifact without affecting image quality or the scan time.

Data Quality and Optimal Background Correction Order of Respiratory-Gated k-Space Segmented Spoiled Gradient Echo (SGRE) and Echo Planar Imaging (EPI)-Based 4D Flow MRI.

BACKGROUND: A reduction in scan time of 4D Flow MRI would facilitate clinical application. A recent study indicates that echo-planar imaging (EPI) 4D Flow MRI allows for a reduction in scan time and better data quality than the recommended k-space segmented spoiled gradient echo (SGRE) sequence. It was argued that the poor data quality of SGRE was related to the nonrecommended absence of respiratory motion compensation. However, data quality can also be affected by the background offset compensation. PURPOSE: To compare the data quality of respiratory motion-compensated SGRE and EPI 4D Flow MRI and their dependence on background correction (BC) order. STUDY TYPE: Retrospective. SUBJECTS: Eighteen healthy subjects (eight female, mean age 32 ± 5 years). FIELD STRENGTH AND SEQUENCE: 1.5 T. [Correction added on July 26, 2019, after first online publication: The preceding field strength was corrected.] SGRE and EPI-based 4D Flow MRI. ASSESSMENT: Data quality was investigated visually and by comparing flows through the cardiac valves and aorta. Measurements were obtained from transvalvular flow and pathline analysis. STATISTICAL TESTS: Linear regression and Bland-Altman analysis were used. Wilcoxon test was used for comparison of visual scoring. Student's t-test was used for comparison of flow volumes. RESULTS: No significant difference was found by visual inspection (P = 0.08). Left ventricular (LV) flows were strongly and very strongly associated with SGRE and EPI, respectively (R2 = 0.86-0.94 SGRE; 0.71-0.79 EPI, BC0-4). LV and right ventricular (RV) outflows and LV pathline flows were very strongly associated (R2 = 0.93-0.95 SGRE; 0.88-0.91 EPI, R2 = 0.91-0.95 SGRE; 0.91-0.93 EPI, BC1-4). EPI LV outflow was lower than the short-axis-based stroke volume. EPI RV outflow and proximal descending aortic flow were lower than SGREs. DATA CONCLUSION: Both sequences yielded good internal data consistency when an adequate background correction was applied. Second and first BC order were considered sufficient for transvalvular flow analysis in SGRE and EPI, respectively. Higher BC orders were preferred for particle tracing. Level of Evidence 4 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2020;51:885-896.

Quantification of epicardial fat using 3D cine Dixon MRI.

BACKGROUND: There is an increased interest in quantifying and characterizing epicardial fat which has been linked to various cardiovascular diseases such as coronary artery disease and atrial fibrillation. Recently, three-dimensional single-phase Dixon techniques have been used to depict the heart and to quantify the surrounding fat. The purpose of this study was to investigate the merits of a new high-resolution cine 3D Dixon technique for quantification of epicardial adipose tissue and compare it to single-phase 3D Dixon in patients with cardiovascular disease. METHODS: Fifteen patients referred for clinical CMR examination of known or suspected heart disease were scanned on a 1.5 T scanner using single-phase Dixon and cine Dixon. Epicardial fat was segmented by three readers and intra- and inter-observer variability was calculated per slice. Cine Dixon segmentation was performed in the same cardiac phase as single-phase Dixon. Subjective image quality assessment of water and fat images were performed by three readers using a 4-point Likert scale (1 = severe; 2 = significant; 3 = mild; 4 = no blurring of cardiac structures). RESULTS: Intra-observer variability was excellent for cine Dixon images (ICC = 0.96), and higher than single-phase Dixon (ICC = 0.92). Inter-observer variability was good for cine Dixon (ICC = 0.76) and moderate for single-phase Dixon (ICC = 0.63). The intra-observer measurement error (mean ± standard deviation) per slice for cine was - 0.02 ± 0.51 ml (- 0.08 ± 0.4%), and for single-phase 0.39 ± 0.72 ml (0.18 ± 0.41%). Inter-observer measurement error for cine was 0.46 ± 0.98 ml (0.11 ± 0.46%) and for single-phase 0.42 ± 1.53 ml (0.17 ± 0.47%). Visual scoring of the water image yielded median of 2 (interquartile range = [Q3-Q1] 2-2) for cine and median of 3 (interquartile range = 3-2) for single-phase (P < 0.05) while no significant difference was found for the fat images, both techniques yielding a median of 3 and interquartile range of 3-2. CONCLUSION: Cine Dixon can be used to quantify epicardial fat with lower intra- and inter-observer variability compared to standard single-phase Dixon. The time-resolved information provided by the cine acquisition appears to support the delineation of the epicardial adipose tissue depot.

Intracardiac Flow at 4D CT: Comparison with 4D Flow MRI.

Purpose To investigate four-dimensional (4D) flow CT for the assessment of intracardiac blood flow patterns as compared with 4D flow MRI. Materials and Methods This prospective study acquired coronary CT angiography and 4D flow MRI data between February and December 2016 in a cohort of 12 participants (age range, 36-74 years; mean age, 57 years; seven men [age range, 36-74 years; mean age, 57 years] and five women [age range, 52-73 years; mean age, 64 years]). Flow simulations based solely on CT-derived cardiac anatomy were assessed together with 4D flow MRI measurements. Flow patterns, flow rates, stroke volume, kinetic energy, and flow components were quantified for both techniques and were compared by using linear regression. Results Cardiac flow patterns obtained by using 4D flow CT were qualitatively similar to 4D flow MRI measurements, as graded by three independent observers. The Cohen κ score was used to assess intraobserver variability (0.83, 0.79, and 0.70) and a paired Wilcoxon rank-sum test showed no significant change (P > .05) between gradings. Peak flow rate and stroke volumes between 4D flow MRI measurements and 4D flow CT measurements had high correlation (r = 0.98 and r = 0.81, respectively; P < .05 for both). Integrated kinetic energy quantified at peak systole correlated well (r = 0.95, P < .05), while kinetic energy levels at early and late filling showed no correlation. Flow component analysis showed high correlation for the direct and residual components, respectively (r = 0.93, P < .05 and r = 0.87, P < .05), while the retained and delayed components showed no correlation. Conclusion Four-dimensional flow CT produced qualitatively and quantitatively similar intracardiac blood flow patterns compared with the current reference standard, four-dimensional flow MRI. © RSNA, 2018 Online supplemental material is available for this article.

Improving left ventricular segmentation in four-dimensional flow MRI using intramodality image registration for cardiac blood flow analysis.

PURPOSE: Assessment of blood flow in the left ventricle using four-dimensional flow MRI requires accurate left ventricle segmentation that is often hampered by the low contrast between blood and the myocardium. The purpose of this work is to improve left-ventricular segmentation in four-dimensional flow MRI for reliable blood flow analysis. METHOD: The left ventricle segmentations are first obtained using morphological cine-MRI with better in-plane resolution and contrast, and then aligned to four-dimensional flow MRI data. This alignment is, however, not trivial due to inter-slice misalignment errors caused by patient motion and respiratory drift during breath-hold based cine-MRI acquisition. A robust image registration based framework is proposed to mitigate such errors automatically. Data from 20 subjects, including healthy volunteers and patients, was used to evaluate its geometric accuracy and impact on blood flow analysis. RESULTS: High spatial correspondence was observed between manually and automatically aligned segmentations, and the improvements in alignment compared to uncorrected segmentations were significant (P < 0.01). Blood flow analysis from manual and automatically corrected segmentations did not differ significantly (P > 0.05). CONCLUSION: Our results demonstrate the efficacy of the proposed approach in improving left-ventricular segmentation in four-dimensional flow MRI, and its potential for reliable blood flow analysis. Magn Reson Med 79:554-560, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Turbulent kinetic energy in the right ventricle: Potential MR marker for risk stratification of adults with repaired Tetralogy of Fallot.

PURPOSE: To assess right ventricular (RV) turbulent kinetic energy (TKE) in patients with repaired Tetralogy of Fallot (rToF) and a spectrum of pulmonary regurgitation (PR), as well as to investigate the relationship between these 4D flow markers and RV remodeling. MATERIALS AND METHODS: Seventeen patients with rToF and 10 healthy controls were included in the study. Patients were divided into two groups based on PR fraction: one lower PR fraction group (≤11%) and one higher PR fraction group (>11%). Field strength/sequences: 3D cine phase contrast (4D flow), 2D cine phase contrast (2D flow), and balanced steady-state free precession (bSSFP) at 1.5T. ASSESSMENT: The RV volume was segmented in the morphologic short-axis images and TKE parameters were computed inside the segmented RV volume throughout diastole. Statistical tests: One-way analysis of variance with Bonferroni post-hoc test; unpaired t-test; Pearson correlation coefficients; simple and stepwise multiple regression models; intraclass correlation coefficient (ICC). RESULTS: The higher PR fraction group had more remodeled RVs (140 ± 25 vs. 107 ± 22 [lower PR fraction, P < 0.01] and 93 ± 15 ml/m2 [healthy, P < 0.001] for RV end-diastolic volume index [RVEDVI]) and higher TKE values (5.95 ± 3.15 vs. 2.23 ± 0.81 [lower PR fraction, P < 0.01] and 1.91 ± 0.78 mJ [healthy, P < 0.001] for Peak Total RV TKE). Multiple regression analysis between RVEDVI and 4D/2D flow parameters showed that Peak Total RV TKE was the strongest predictor of RVEDVI (R2 = 0.47, P = 0.002). CONCLUSION: The 4D flow-specific TKE markers showed a slightly stronger association with RV remodeling than conventional 2D flow PR parameters. These results suggest novel hemodynamic aspects of PR in the development of late complications after ToF repair. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1043-1053.

Longitudinal changes in myocardial T1 and T2 relaxation times related to diffuse myocardial fibrosis in aortic stenosis; before and after aortic valve replacement.

BACKGROUND: Diffuse myocardial fibrosis is associated with adverse outcomes, although detection and quantification is challenging. Cardiac MR relaxation times mapping represents a promising imaging biomarker for diffuse myocardial fibrosis. PURPOSE: To investigate whether relaxation times can detect longitudinal changes in myocardial tissue composition associated with diffuse fibrosis in patients with severe aortic stenosis (AS) before and after aortic valve replacement (AVR). STUDY TYPE: Prospective longitudinal study. POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: Fifteen patients with severe AS. FIELD STRENGTH/SEQUENCE: 3T / 3(3)3(3)5-MOLLI, T2 -GraSE, and 3D-QALAS. ASSESSMENT: Patients underwent MR examinations at three timepoints: before AVR, as well as 3 and 12 months after AVR. Data from each patient was analyzed in 16 myocardial segments. STATISTICAL TESTS: The segment-wise T1 and T2 data were analyzed over time after surgery using linear mixed models for repeated measures analysis. RESULTS: The results showed that T1 relaxation times were significantly (P < 0.05) shorter 3 and 12 months postoperative than preoperative and that the T2 relaxation times were significantly (P < 0.05) longer 3 and 12 months postoperative than preoperative for both 3D and 2D mapping methods. No significant changes were seen between 3 and 12 months postoperative for any of the methods (P = 0.06/0.19 for T1 with 3D-QALAS/MOLLI and P = 0.09/0.25 for T2 with 3D-QALAS/GraSE). DATA CONCLUSION: We demonstrated that changes in myocardial relaxation times and thus tissue characteristics can be observed within 3 months after AVR surgery. The significant changes in relaxation times from preoperative examinations to the follow-up may be interpreted as a reduction of interstitial fibrosis in the left ventricular wall. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018.

Test-retest variability of left ventricular 4D flow cardiovascular magnetic resonance measurements in healthy subjects.

BACKGROUND: Quantification and visualisation of left ventricular (LV) blood flow is afforded by three-dimensional, time resolved phase contrast cardiovascular magnetic resonance (CMR 4D flow). However, few data exist upon the repeatability and variability of these parameters in a healthy population. We aimed to assess the repeatability and variability over time of LV 4D CMR flow measurements. METHODS: Forty five controls underwent CMR 4D flow data acquisition. Of these, 10 underwent a second scan within the same visit (scan-rescan), 25 returned for a second visit (interval scan; median interval 52 days, IQR 28-57 days). The LV-end diastolic volume (EDV) was divided into four flow components: 1) Direct flow: inflow that passes directly to ejection; 2) Retained inflow: inflow that enters and resides within the LV; 3) Delayed ejection flow: starts within the LV and is ejected and 4) Residual volume: blood that resides within the LV for > 2 cardiac cycles. Each flow components' volume was related to the EDV (volume-ratio). The kinetic energy at end-diastole (ED) was measured and divided by the components' volume. RESULTS: The dominant flow component in all 45 controls was the direct flow (volume ratio 38 ± 4%) followed by the residual volume (30 ± 4%), then delayed ejection flow (16 ± 3%) and retained inflow (16 ± 4%). The kinetic energy at ED for each component was direct flow (7.8 ± 3.0 microJ/ml), retained inflow (4.1 ± 2.0 microJ/ml), delayed ejection flow (6.3 ± 2.3 microJ/ml) and the residual volume (1.2 ± 0.5 microJ/ml). The coefficients of variation for the scan-rescan ranged from 2.5%-9.2% for the flow components' volume ratio and between 13.5%-17.7% for the kinetic energy. The interval scan results showed higher coefficients of variation with values from 6.2-16.1% for the flow components' volume ratio and 16.9-29.0% for the kinetic energy of the flow components. CONCLUSION: LV flow components' volume and their associated kinetic energy values are repeatable and stable within a population over time. However, the variability of these measurements in individuals over time is greater than can be attributed to sources of error in the data acquisition and analysis, suggesting that additional physiological factors may influence LV flow measurements.