Usformer: A small network for left atrium segmentation of 3D LGE MRI.

Left atrial (LA) fibrosis plays a vital role as a mediator in the progression of atrial fibrillation. 3D late gadolinium-enhancement (LGE) MRI has been proven effective in identifying LA fibrosis. Image analysis of 3D LA LGE involves manual segmentation of the LA wall, which is both lengthy and challenging. Automated segmentation poses challenges owing to the diverse intensities in data from various vendors, the limited contrast between LA and surrounding tissues, and the intricate anatomical structures of the LA. Current approaches relying on 3D networks are computationally intensive since 3D LGE MRIs and the networks are large. Regarding this issue, most researchers came up with two-stage methods: initially identifying the LA center using a scaled-down version of the MRIs and subsequently cropping the full-resolution MRIs around the LA center for final segmentation. We propose a lightweight transformer-based 3D architecture, Usformer, designed to precisely segment LA volume in a single stage, eliminating error propagation associated with suboptimal two-stage training. The transposed attention facilitates capturing the global context in large 3D volumes without significant computation requirements. Usformer outperforms the state-of-the-art supervised learning methods in terms of accuracy and speed. First, with the smallest Hausdorff Distance (HD) and Average Symmetric Surface Distance (ASSD), it achieved a dice score of 93.1% and 92.0% in the 2018 Atrial Segmentation Challenge and our local institutional dataset, respectively. Second, the number of parameters and computation complexity are largely reduced by 2.8x and 3.8x, respectively. Moreover, Usformer does not require a large dataset. When only 16 labeled MRI scans are used for training, Usformer achieves a 92.1% dice score in the challenge dataset. The proposed Usformer delineates the boundaries of the LA wall relatively accurately, which may assist in the clinical translation of LA LGE for planning catheter ablation of atrial fibrillation.

PYCR1, BANF1, and STARD8 Expression in Gastric Carcinoma: A Clinicopathologic, Prognostic, and Immunohistochemical Study.

BACKGROUND: It will be important to understand the molecular pathways of gastric cancer (GC) occurrence and progression, thus detecting predictive and prognostic biomarkers of GC. Pyrroline-5-carboxylate reductase 1 (PYCR1) was upregulated in many cancers, suggesting its possible roles in carcinogenesis and tumor metastases. Barrier-of-autointegration factor 1 (BANF1) is a protein family that plays essential roles in maintaining the integrity of an intact cellular genome. Rho-GTPs are molecular switches that control many signal transduction pathways in normal cells, including 3 subgroups from 1 to 3 (DLC1-3). DLC-3, known as StAR-related lipid transfer domain protein 8 (STARD8), and its role in cancers were not sufficiently studied. The study aimed to investigate the significance of PYCR1, BANF1, and STARD8 protein expression in GC tissues and normal gastric mucosa retrieved from patients with GC to detect prognostic roles of expression. PATIENTS AND METHODS: Specimens were collected from 100 patients with gastric carcinoma. After the application of the inclusion criteria of the study, we prepared 100 paraffin blocks from samples of the 100 included patients; each block included samples from gastric carcinoma and adjacent non-neoplastic gastric mucosa. We assessed the expression of PYCR1, BANF1, and STARD8 using immunohistochemistry in all studied samples. We followed patients for the detection of disease progression and survival rates. We correlate PYCR1, BANF1, and STARD8 expression with clinical, pathologic, and prognostic parameters. RESULTS: Overexpression of PYCR1 and BANF1 and decreased expression of STARD8 was found in gastric carcinoma tissues than adjacent non-neoplastic gastric mucosa ( P <0.001), and was positively associated with high grade ( P =0.006), depth of tumor invasion, presence of lymph nodes metastases and advanced stage ( P =0.001), high incidence of GC progression, recurrence, unfavorable disease-free survival ( P =0.003) and unfavorable overall survival rates ( P <0.001). Thus, it was revealed that; in univariate and multivariate analyses, levels of PYCR1, BANF1, and STARD8 are associated with the overall survival rate of GC patients. CONCLUSIONS: We showed that overexpression of PYCR1 and BANF1 and decreased expression of STARD8 in GC tissues was associated with poor prognosis and GC progression.

Robust and fast stochastic 4D flow vector-field signature technique for quantifying composite flow dynamics from 4D flow MRI: Application to left atrial flow in atrial fibrillation.

4D flow MRI is an emerging imaging modality that maps voxel-wise blood flow information as velocity vector fields that is acquired in 7-dimensional image volumes (3 spatial dimensions + 3 velocity directions + time). Blood flow in the cardiovascular system is often complex and composite involving multiple flow dynamics and patterns (e.g., vortex flow, jets, stagnating flow) that occur and interact simultaneously. The spectrum of such complex flow dynamics is embedded in the velocity vector field dynamics derived from 4D Flow MRI. However, current flow metrics cannot fully measure high-dimensional vector-field data and embedded complex composite flow data. Instead, these methods need to break down the vector-field data into secondary scalar fields of individual flow components using fluid dynamics operators. These methods are gradient-based and sensitive to data uncertainties, and only focus on individual flow components of the overall composite flow, therefore potentially underestimating the severity of overall flow changes associated with cardiovascular diseases. To address these limitations, in MICCAI 2021, we introduced a novel comprehensive stochastic 4D Flow vector-field signature technique that works directly on the entire spatiotemporal velocity vector field. This technique uses efficient stochastic gradient-free interrogation of multi-million flow vector-pairs per patient to derive the patient's unique flow profile of the complex composite flow alterations and in real-time processing. The signature technique's probabilistic gradient-free formulation should allow for highly robust quantification despite inherent errors in 4D flow MRI acquisitions. Here, we extend the application of the 4D flow vector-field signature technique to the left atrium to analyze complex composite flow changes in patients with atrial fibrillation. In 128 subjects, we performed extensive sensitivity testing and determined that the vector-field signature technique is highly robust to typical sources of data uncertainties in 4D flow MRI: degradation in spatiotemporal resolution, added Gaussian noise, and segmentation errors. We demonstrate the excellent generalizability of the stochastic convergence from the aorta to the left atrium and between different 4D Flow MRI acquisition protocols. We compare the robustness of our technique to existing advanced flow quantification metrics of kinetic energy, vorticity, and energy loss demonstrating a superior performance of up-to 14-fold. Our results show the potential diagnostic and clinical utility of our signature technique in identifying distinctly altered composite flow signatures in atrial fibrillation patients independent of existing flow metrics.

Valvular and ascending aortic hemodynamics of the On-X aortic valved conduit by same-day echocardiography and 4D flow MRI.

This study aims to assess whether the On-X aortic valved conduit better restores normal valvular and ascending aortic hemodynamics than other commonly used bileaflet mechanical valved conduit prostheses from St. Jude Medical and Carbomedics by using same-day transthoracic echocardiography (TTE) and 4D flow magnetic resonance imaging (MRI) examinations. TTE and 4D flow MRI were performed back-to-back in 10 patients with On-X, six patients with St. Jude (two) and Carbomedics (four) prostheses, and 36 healthy volunteers. TTE evaluated valvular hemodynamic parameters: transvalvular peak velocity (TPV), mean and peak transvalvular pressure gradient (TPG), and effective orifice area (EOA). 4D flow MRI evaluated the peak systolic 3D viscous energy loss rate (VELR) density and mean vorticity magnitude in the ascending aorta (AAo). While higher TPV and mean and peak TPG were recorded in all patients compared to healthy subjects, the values in On-X patients were closer to those in healthy subjects (TPV 1.9 ± 0.3 vs. 2.2 ± 0.3 vs. 1.2 ± 0.2 m/s, mean TPG 7.4 ± 1.9 vs. 9.2 ± 2.3 vs. 3.1 ± 0.9 mmHg, peak TPG 15.3 ± 5.2 vs. 18.9 ± 5.2 vs. 6.1 ± 1.8 mmHg, p < 0.001). Likewise, while higher VELR density and mean vorticity magnitude were recorded in all patients than in healthy subjects, the values in On-X patients were closer to those in healthy subjects (VELR: 50.6 ± 20.1 vs. 89.8 ± 35.2 vs. 21.4 ± 9.2 W/m3, p < 0.001) and vorticity (147.6 ± 30.0 vs. 191.2 ± 26.0 vs. 84.6 ± 20.5 s-1, p < 0.001). This study demonstrates that the On-X aortic valved conduit may produce less aberrant hemodynamics in the AAo while maintaining similar valvular hemodynamics to St. Jude Medical and Carbomedics alternatives.

MRI Quantification of Left Atrial Circumferential Strain in Mitral Regurgitation: A Feasibility and Reproducibility Study.

BACKGROUND: MRI-derived left atrial (LA) longitudinal strain has been shown to be a marker for mitral regurgitation, but the utility of LA circumferential strain remains unclear. PURPOSE: To assess feasibility and reproducibility of LA circumferential strain, identify changes in mitral regurgitation patients compared to healthy volunteers, and determine strain's association with mitral regurgitation severity and cardiac function. STUDY TYPE: Retrospective. POPULATION: 52 mitral regurgitation patients, 12 healthy volunteers. FIELD STRENGTH/SEQUENCE: Steady-state free precession cine and 2D phase contrast sequences at 1.5T. ASSESSMENT: Peak LA circumferential strain was computed in each of three short-axis slices (superior, mid, and inferior) and longitudinal strain computed from long-axis slices using MRI feature-tracking software. Strain test-retest reproducibility was determined from two repeat studies in healthy volunteers. STATISTICAL TESTS: LA circumferential strain test-retest reproducibility was assessed by intra-class correlation coefficient (ICC). Strain was compared between cohorts using Student's t-test or Mann-Whitney U. Mitral regurgitation severity association with strain and LV function was assessed using Spearman correlation and multivariable regression. Significance was defined as P < 0.05. RESULTS: LA circumferential strain assessment was feasible in all subjects with moderate reproducibility in the superior (ICC = 0.74), mid LA (ICC = 0.71), and inferior LA (ICC = 0.63). In mitral regurgitation patients, LA circumferential strain was significantly lower in the superior (11.86% [6.5%,19.2%] vs. 18.73% ± 6.7%) and mid LA slices (18.41% ± 9.5% vs. 28.7% ± 10.4%) compared to healthy volunteers. Mitral regurgitation severity significantly associated with mid LA circumferential strain (ß = -0.03) and LAV significantly associated with superior LA circumferential strain (ß = -2.09), both independent of LA longitudinal strain and CO. DATA CONCLUSION: LA circumferential strain assessment is feasible with moderate reproducibility. Compared to healthy volunteers, patients had significantly lower LA circumferential strain. Mitral regurgitation severity and LAV were significantly associated with LA circumferential strain independent of LA longitudinal strain. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Four-dimensional magnetic resonance after ascending aorta replacement and aortic valve repair with HAART 300 internal annuloplasty ring.

BACKGROUND: The hemispherical aortic annuloplasty reconstructive technology (HAART) is an internal geometric annuloplasty ring designed to restore a natural elliptical shape to the aortic annulus as part of aortic valve repair. We present four-dimensional flow hemodynamic analysis before and after implementation of the HAART ring in patients undergoing ascending aortic replacement. METHODS: Aortic hemodynamics over the cardiac cycle were visualized using time-resolved three-dimensional pathlines. Velocity streamlines tangent to the time-resolved velocity vector field were used to demonstrate instantaneous aortic hemodynamics. Peak velocities, forward and retrograde flow were calculated at nine planes placed along the midline of the thoracic aorta. Systolic wall shear stress and peak viscous energy loss over the cardiac cycle were calculated. RESULTS: HAART patients displayed similar or improved flow profiles after surgery when compared to a patient undergoing ascending aortic replacement alone. CONCLUSION: There may be a trend towards improved flow dynamics in patients undergoing HAART ring implantation.

Albuminuria as a predictor of mortality in type II diabetic patients after living-donor liver transplantation.

PURPOSE: Diabetes mellitus (DM) increases the risk of morbidity and mortality after liver resection. Albuminuria is associated with a higher risk for all-cause and cardiovascular mortality. This study evaluated albuminuria as a predictor of the outcome of living donor liver transplantation (LDLT) in patients with pre-existing DM. METHODS: This retrospective study involved 103 type II diabetic patients with end-stage liver disease who received LDLT. Preoperative spot urine albumin: creatinine ratio was used to determine the degree of albuminuria. The primary outcome measure was the impact of urinary albumin excretion on the 3-year mortality rate after LDLT in this diabetic cohort. RESULTS: Hepatitis C virus infection was the main cause of cirrhosis. Albuminuria was detected in 41 patients (39.8%); 15 had macroalbuminuria, while 26 had microalbuminuria. Patients with microalbuminuria were significantly older than those with macroalbuminuria and normal albumin in urine. After 3 years, twenty-four patients (23.3%) died within 3 years after LT. Myocardial infarction was the leading cause of death (25%). Albuminuria was an independent factor affecting 3-year mortality with an odds ratio of 5.17 (95% CI: 1.86-14.35). CONCLUSION: Preoperative albuminuria is an independent factor affecting mortality within 3 years after LDLT in type II diabetic patients. Myocardial infarction was the leading cause of death in 25% of cases, followed by hepatocellular carcinoma recurrence, sepsis, and graft failure.KEY MESSAGESDiabetes mellitus (DM) increases the risk of morbidity and mortality after liver resection.Albuminuria is associated with a higher risk for all-cause and cardiovascular mortality.Preoperative albuminuria is a significant predictor of mortality within 3 years after LDLT in diabetic patients.

Left ventricular four-dimensional blood flow distribution, energetics, and vorticity in chronic myocardial infarction patients with/without left ventricular thrombus.

BACKGROUND: Left ventricular thrombus (LVT) formation is a frequent and serious complication of myocardial infarction (MI). How global LV flow characteristics are related to this phenomenon is yet uncertain. In this study, we investigated LV flow differences using 4D flow cardiovascular magnetic resonance (CMR) between chronic MI patients with LVT [MI-LVT(+)] and without LVT [MI-LVT(-)], and healthy controls. METHODS: In this prospective cohort study, the 4D flow CMR data were acquired in 19 chronic MI patients (MI-LVT(+), n = 9 and MI-LVT(-), n = 10) and 9 age-matched controls. All included subjects were in sinus rhythm. The following LV flow parameters were obtained: LV flow components (direct, retained, delayed, residual), mean and peak kinetic energy (KE) values (indexed to instantaneous LV volume), mean and peak vorticity values, and diastolic vortex ring properties (position, orientation, shape). RESULTS: The MI patients demonstrated a significantly larger amount of delayed and residual flow, and a smaller amount of direct flow compared to controls (p = 0.02, p = 0.03, and p < 0.001, respectively). The MI-LVT(+) patients demonstrated numerically increased residual flow and reduced retained and direct flow in comparison to MI-LVT(-) patients. Systolic mean and peak LV blood flow KE values were significantly lower in MI patients compared to controls (p = 0.04, p = 0.03, respectively). Overall, the mean and peak LV vorticity values were significantly lower in MI patients compared to controls. The mean and peak systolic vorticity at the basal level were significantly higher in MI-LVT(+) than in MI-LVT(-) patients (p < 0.01, for both). The vortex ring core during E-wave in MI-LVT(+) group was located in a less tilted orientation to the LV compared to MI-LVT(-) group (p < 0.01). CONCLUSIONS: Chronic MI patients with LVT express a different distribution of LV flow components, irregular vorticity vector fields, and altered diastolic vortex ring geometric properties as assessed by 4D flow CMR. Larger prospective studies are warranted to further evaluate the significance of these initial observations.

Aortic Pulse Wave Velocity Evaluated by 4D Flow MRI Across the Adult Lifespan.

BACKGROUND: Evaluation of aortic stiffness by pulse wave velocity (PWV) across the adult lifespan is needed to better understand normal aging in women and men. PURPOSE: To characterize PWV in the thoracic aorta using 4D flow MRI in an age- and sex-stratified cohort of healthy adults. STUDY TYPE: Retrospective. POPULATION: Ninety nine healthy participants (age: 46 ± 15 [19-79] years, 50% female), divided into young adults (<45 years) (N = 48), midlife (45-65 years) (N = 37), and later life (>65 years) (N = 14) groups. FIELD STRENGTH/SEQUENCE: 1.5 T or 3 T, 2D cine bSSFP, 4D flow MRI. ASSESSMENT: Cardiac functional parameters of end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and myocardial mass were assessed by 2D cine bSSFP. PWV and aortic blood flow velocity were assessed by 4D flow MRI. Reproducibility of PWV was evaluated in a subset of nine participants. STATISTICAL TESTS: Analysis of variance, Pearson's correlation coefficient (r), linear regression, intraclass correlation coefficient (ICC). A P value < 0.05 was considered statistically significant. RESULTS: PWV increased significantly with age (young adults: 5.4 ± 0.9 m/sec, midlife: 7.2 ± 1.1 m/sec, and later life: 9.4 ± 1.8 m/sec) (r = 0.79, slope = 0.09 m/sec/year). PWV did not differ in women and men in entire sample (P = 0.40) or within age groups (young adults: P = 0.83, midlife: P = 0.17, and later life: P = 0.96). PWV was significantly correlated with EDV (r = -0.29), ESV (r = -0.23), SV (r = -0.28), myocardial mass (r = 0.21), and mean aortic blood flow velocity (r = -0.62). In the test-retest subgroup (N = 9), PWV was 6.7 ± 1.5 [4.4-9.3] m/sec and ICC = 0.75. DATA CONCLUSION: 4D flow MRI quantified higher aortic PWV with age, by approximately 1 m/sec per decade, and significant differences between young adults, midlife and later life. Reproducibility analysis showed good test-retest agreement. Increased PWV was associated with decline in cardiac function and reduced aortic blood flow velocity. This study demonstrates the utility of 4D flow MRI-derived aortic PWV for studying aging. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Direct mitral regurgitation quantification in hypertrophic cardiomyopathy using 4D flow CMR jet tracking: evaluation in comparison to conventional CMR.

BACKGROUND: Quantitative evaluation of mitral regurgitation (MR) in hypertrophic cardiomyopathy (HCM) by cardiovascular magnetic resonance (CMR) relies on an indirect volumetric calculation. The aim of this study was to directly assess and quantify MR jets in patients with HCM using 4D flow CMR jet tracking in comparison to standard-of-care CMR indirect volumetric method. METHODS: This retrospective study included patients with HCM undergoing 4D flow CMR. By the indirect volumetric method from CMR, MR volume was quantified as left ventricular stroke volume minus forward aortic volume. By 4D flow CMR direct jet tracking, multiplanar reformatted planes were positioned in the peak velocity of the MR jet during systole to calculate through-plane regurgitant flow. MR severity was collected for agreement analysis from a clinical echocardiograms performed within 1 month of CMR. Inter-method and inter-observer agreement were assessed by intraclass correlation coefficient (ICC), Bland-Altman analysis, and Cohen's kappa. RESULTS: Thirty-seven patients with HCM were included. Direct jet tracking demonstrated good inter-method agreement of MR volume compared to the indirect volumetric method (ICC = 0.80, p = 0.004) and fair agreement of MR severity (kappa = 0.27, p = 0.03). Direct jet tracking showed higher agreement with echocardiography (kappa = 0.35, p = 0.04) than indirect volumetric method (kappa = 0.16, p = 0.35). Inter-observer reproducibility of indirect volumetric method components revealed the lowest reproducibility in end-systolic volume (ICC = 0.69, p = 0.15). Indirect volumetric method showed good agreement of MR volume (ICC = 0.80, p = 0.003) and fair agreement of MR severity (kappa = 0.38, p < 0.001). Direct jet tracking demonstrated (1) excellent inter-observer reproducibility of MR volume (ICC = 0.97, p < 0.001) and MR severity (kappa = 0.84, p < 0.001) and (2) excellent intra-observer reproducibility of MR volume (ICC = 0.98, p < 0.001) and MR severity (kappa = 0.88, p < 0.001). CONCLUSIONS: Quantifying MR and assessing MR severity by indirect volumetric method in HCM patients has limited inter-observer reproducibility. 4D flow CMR jet tracking is a potential alternative technique to directly quantify and assess MR severity with excellent inter- and intra-observer reproducibility and higher agreement with echocardiography in this population.

Hemodynamic interplay of vorticity, viscous energy loss, and kinetic energy from 4D Flow MRI and link to cardiac function in healthy subjects and Fontan patients.

The purpose of this study was to directly assess (patho)physiology of intraventricular hemodynamic interplay between four-dimensional flow cardiovascular magnetic resonance imaging (4D Flow MRI)-derived vorticity with kinetic energy (KE) and viscous energy loss (EL) over the cardiac cycle and their association to ejection fraction (EF) and stroke volume (SV). Fifteen healthy subjects and thirty Fontan patients underwent whole heart 4D Flow MRI. Ventricular vorticity, KE, and EL were computed over systole (vorticity_volavg systole, KEavg systole, and ELavg systole) and diastole (vorticity_volavg diastole, KEavg diastole, and ELavg diastole). The association between vorticity_vol and KE and EL was tested by Spearman correlation. Fontan patients were grouped to normal and impaired EF groups. A significant correlation was found between SV and vorticity in healthy subjects (systolic: ρ = 0.84, P < 0.001; diastolic: ρ = 0.81, P < 0.001) and in Fontan patients (systolic: ρ = 0.61, P < 0.001; diastolic: ρ = 0.54, P = 0.002). Healthy subjects showed positive correlation between vorticity_vol versus KE (systole: ρ = 0.96, P < 0.001; diastole: ρ = 0.90, P < 0.001) and EL (systole: ρ = 0.85, P < 0.001; diastole: ρ = 0.84, P < 0.001). Fontan patients showed significantly elevated vorticity_vol compared with healthy subjects (vorticity_volavg systole: 3.1 [2.3-3.9] vs. 1.7 [1.3-2.4] L/s, P < 0.001; vorticity_volavg diastole: 3.1 [2.0-3.7] vs. 2.1 [1.6-2.8] L/s, P = 0.002). This elevated vorticity in Fontan patients showed strong association with KE (systole: ρ = 0.91, P < 0.001; diastole: ρ = 0.85, P < 0.001) and EL (systole: ρ = 0.82, P < 0.001; diastole: ρ = 0.89, P < 0.001). Fontan patients with normal EF showed significantly higher vorticity_volavg systole and ELavg systole, but significantly decreased KE avg diastole, in the presence of normal SV, compared with healthy subjects. Healthy subjects show strong physiological hemodynamic interplay between vorticity with KE and EL. Fontan patients demonstrate a pathophysiological hemodynamic interplay characterized by correlation of elevated vorticity with KE and EL in the presence of maintained normal stroke volume. Altered vorticity and energetic hemodynamics are found in the presence of normal EF in Fontan patients.NEW & NOTEWORTHY Physiologic intraventricular hemodynamic interplay/coupling is present in the healthy left ventricle between vorticity versus viscous energy loss and kinetic energy from four-dimensional flow cardiovascular magnetic resonance imaging (4D Flow MRI). Conversely, Fontan patients present compensatory pathophysiologic hemodynamic coupling by an increase in intraventricular vorticity that positively correlates to viscous energy loss and kinetic energy levels in the presence of maintained normal stroke volume. Altered vorticity and energetics are found in the presence of normal ejection fraction in Fontan patients.

4D flow MRI left atrial kinetic energy in hypertrophic cardiomyopathy is associated with mitral regurgitation and left ventricular outflow tract obstruction.

To noninvasively assess left atrial (LA) kinetic energy (KE) in hypertrophic cardiomyopathy (HCM) patients using 4D flow MRI and evaluate coupling associations with mitral regurgitation (MR) and left ventricular outflow tract (LVOT) obstruction. Twenty-nine retrospectively identified patients with HCM underwent 4D flow MRI. MRI-estimated peak LVOT pressure gradient (∆PMRI) was used to classify patients into non-obstructive and obstructive HCM. Time-resolved volumetric LA kinetic energy (KELA) was computed throughout systole. Average systolic (KELA-avg) and peak systolic (KELA-peak) KELA were compared between non-obstructive and obstructive HCM groups, and associations to MR severity and LVOT ∆PMRI were tested.The study included 15 patients with non-obstructive HCM (58.6 [45.9, 65.2] years, 7 females) and 14 patients with obstructive HCM (51.9 [47.6, 62.6] years, 6 females). Obstructive HCM patients demonstrated significantly elevated instantaneous KELA over all systolic time-points compared to non-obstructive HCM (P < 0.05). Obstructive HCM patients also demonstrated higher KELA-avg (14.8 [10.6, 20.4] J/m3 vs. 33.4 [23.9, 61.3] J/m3, P < 0.001) and KELA-peak (22.1 [15.9, 28.7] J/m3 vs. 57.2 [44.5, 121.4] J/m3, P < 0.001) than non-obstructive HCM. MR severity was significantly correlated with KELA-avg (rho = 0.81, P < 0.001) and KELA-peak (rho = 0.79, P < 0.001). LVOT ∆PMRI was strongly correlated with KELA metrics in obstructive HCM (KELA-avg: rho = 0.86, P < 0.001; KELA-peak: rho = 0.85, P < 0.001).In HCM patients, left atrial kinetic energy, by 4D flow MRI, is associated with MR severity and the degree of LVOT obstruction.

Intracardiac and Vascular Hemodynamics with Cardiovascular Magnetic Resonance in Heart Failure.

In heart failure (HF), the impaired heart loses its ability to competently eject blood during systole or fill with blood during diastole, manifesting in multifaceted abnormal intracardiac or intravascular flow dynamics. Conventional imaging techniques are limited in their ability to evaluate multidirectional multidimensional flow alterations in HF. Four-dimensional (4-D) flow magnetic resonance imaging (MRI) has emerged as a promising technique to comprehensively visualize and quantify changes in 3-dimensional blood flow dynamics in complex cardiovascular diseases. This article reviews emerging applications of 4-D flow MRI hemodynamic markers in HF and etiologies at risk of progressing to HF.

Impact of age, sex, and global function on normal aortic hemodynamics.

PURPOSE: To examine the effects of age, sex, and left ventricular global function on velocity, helicity, and 3D wall shear stress (3D-WSS) in the aorta of N = 100 healthy controls. METHODS: Fifty female and 50 male volunteers with no history of cardiovascular disease, with 10 volunteers per age group (18-30, 31-40, 41-50, 51-60, and 61-80 years) underwent aortic 4D-flow MRI. Quantification of systolic aortic peak velocity, helicity, and 3D-WSS distribution and the calculation of age group-averaged peak systolic velocity and 3D-WSS maps ("atlases") were computed. Age-related and sex-related changes in peak velocity, helicity, and 3D-WSS were computed and correlated with standard metrics of left ventricular function derived from short-axis cine MRI. RESULTS: No significant differences were found in peak systolic velocity or 3D-WSS based on sex except for the 18- to 30-year-old group (males 8% higher velocity volume and 3D-WSS surface area). Between successively older groups, systolic velocity decreased (13%, <1%, 7%, and 55% of the aorta volume) and 3D-WSS decreased (21%, 2%, 30%, and 62% of the aorta surface area). Mean velocity, mean 3D-3D-WSS, and median helicity increased with cardiac output (r = 0.27-0.43, all P < .01), and mean velocity and 3D-WSS decreased with increasing diameter (r > 0.35, P < .001). Arch and descending aorta systolic mean velocity, mean 3D-WSS, and median helicity increased with normalized left ventricular volumes: end diastolic volume (r = 0.31-0.37, P < .01), end systolic volume (r = 0.27-0.35, P < .01), and stroke volume (r = 0.28-0.35, P < .01). CONCLUSION: Healthy aortic hemodynamics are dependent on subject age, and correlate with vessel diameter and cardiac function.

Fully automated 3D aortic segmentation of 4D flow MRI for hemodynamic analysis using deep learning.

PURPOSE: To generate fully automated and fast 4D-flow MRI-based 3D segmentations of the aorta using deep learning for reproducible quantification of aortic flow, peak velocity, and dimensions. METHODS: A total of 1018 subjects with aortic 4D-flow MRI (528 with bicuspid aortic valve, 376 with tricuspid aortic valve and aortic dilation, 114 healthy controls) comprised the data set. A convolutional neural network was trained to generate 3D aortic segmentations from 4D-flow data. Manual segmentations served as the ground truth (N = 499 training, N = 101 validation, N = 418 testing). Dice scores, Hausdorff distance, and average symmetrical surface distance were calculated to assess performance. Aortic flow, peak velocity, and lumen dimensions were quantified at the ascending, arch, and descending aorta and compared using Bland-Altman analysis. Interobserver variability of manual analysis was assessed on a subset of 40. RESULTS: Convolutional neural network segmentation required 0.438 ± 0.355 seconds versus 630 ± 254 seconds for manual analysis and demonstrated excellent performance with a median Dice score of 0.951 (0.930-0.966), Hausdorff distance of 2.80 (2.13-4.35), and average symmetrical surface distance of 0.176 (0.119-0.290). Excellent agreement was found for flow, peak velocity, and dimensions with low bias and limits of agreement less than 10% difference versus manual analysis. For aortic volume, limits of agreement were moderate within 16.3%. Interobserver variability (median Dice score: 0.950; Hausdorff distance: 2.45; and average symmetrical surface distance: 0.145) and convolutional neural network-based analysis (median Dice score: 0.953-0.959; Hausdorff distance: 2.24-2.91; and average symmetrical surface distance: 0.145-1.98 to observers) demonstrated similar reproducibility. CONCLUSIONS: Deep learning enabled fast and automated 3D aortic segmentation from 4D-flow MRI, demonstrating its potential for efficient clinical workflows. Future studies should investigate its utility for other vasculature and multivendor applications.

Clinical assessment of aortic valve stenosis: Comparison between 4D flow MRI and transthoracic echocardiography.

BACKGROUND: The prevalence of valvular aortic stenosis (AS) increases as the population ages. Echocardiographic measurements of peak jet velocity (Vpeak ), mean pressure gradient (Pmean ), and aortic valve area (AVA) determine AS severity and play a pivotal role in the stratification towards valvular replacement. A multimodality imaging approach might be needed in cases of uncertainty about the actual severity of the stenosis. PURPOSE: To compare four-dimensional phase-contrast magnetic resonance (4D PC-MR), two-dimensional (2D) PC-MR, and transthoracic echocardiography (TTE) for quantification of AS. STUDY TYPE: Prospective. POPULATION: Twenty patients with various degrees of AS (69.3 ± 5.0 years). FIELD STRENGTH/SEQUENCES: 4D PC-MR and 2D PC-MR at 3T. ASSESSMENT: We compared Vpeak , Pmean , and AVA between TTE, 4D PC-MR, and 2D PC-MR. Flow eccentricity was quantified by means of normalized flow displacement, and its influence on the accuracy of TTE measurements was investigated. STATISTICAL TESTS: Pearson's correlation, Bland-Altman analysis, paired t-test, and intraclass correlation coefficient. RESULTS: 4D PC-MR measured higher Vpeak (r = 0.95, mean difference + 16.4 ± 10.7%, P <0.001), and Pmean (r = 0.92, mean difference + 14.9 ± 16.0%, P = 0.013), but a less critical AVA (r = 0.80, mean difference + 19.9 ± 20.6%, P = 0.002) than TTE. In contrast, unidirectional 2D PC-MR substantially underestimated AS severity when compared with TTE. Differences in Vpeak between 4D PC-MR and TTE showed to be strongly correlated with the eccentricity of the flow jet (r = 0.89, P <0.001). Use of 4D PC-MR improved the concordance between Vpeak and AVA (from 0.68 to 0.87), and between PGmean and AVA (from 0.68 to 0.86). DATA CONCLUSION: 4D PC-MR improves the concordance between the different AS parameters and could serve as an additional imaging technique next to TTE. Future studies should address the potential value of 4D PC-MR in patients with discordant echocardiographic parameters. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:472-480.

Four-dimensional Virtual Catheter: Noninvasive Assessment of Intra-aortic Hemodynamics in Bicuspid Aortic Valve Disease.

Background Four-dimensional (4D) flow MRI enables the evaluation of blood flow alterations in patients with congenital bicuspid aortic valve (BAV). However, current analysis methods are cumbersome and lack the use of the volumetric data from 4D MRI. Purpose To investigate the feasibility and reproducibility of a technique that uses a catheter-like mathematical model (virtual catheter) to assess volumetric intra-aortic hemodynamics from 4D flow MRI in patients with BAV. Materials and Methods In this retrospective study, data were collected from adult patients with BAV and healthy participants who underwent aortic 4D flow MRI from November 2011 through August 2014. Reproducibility was tested in healthy study participants who underwent test-retest examinations within 2 weeks. Patients were grouped on the basis of the severity of aortic valve regurgitation (AVR) and aortic valve stenosis (AVS). A 4D virtual catheter mathematical model for probing intra-aortic hemodynamic flow was constructed as a tube with an automatically derived radius along the entire thoracic aorta centerline. Volumetric intra-aortic hemodynamics were computed from 4D flow MRI only within the virtual catheter, and the following volume-normalized systolic peaks were derived: kinetic energy (KE), viscous energy loss rate (VELR), and vorticity. Hemodynamic data were presented as medians with interquartile ranges and compared by using Mann-Whitney U test and Kruskal-Wallis test. Results The study included 91 participants (57 patients [mean age, 46 years ± 12], 18 women; 34 healthy participants [mean age: 44 years ± 14], 12 women; 15 healthy participants underwent test-retest examinations). Patients showed higher VELR values compared with healthy participants (median, 31 W/m3 [interquartile range, 21-72] vs 23 W/m3 [interquartile range, 17-30], respectively; P < .001) and vorticity (69 sec-1 [interquartile range, 59-87] vs 60 sec-1 [interquartile range, 50-67], respectively; P < .001). Four-dimensional virtual catheter showed differences among different AVS and AVR grades with the highest VELR (120 W/m3; interquartile range, 99-166; P < .001) and vorticity (108 sec-1; interquartile range, 84-151; P < .001) found in severe AVS. High test-retest reproducibility was found for all virtual catheter-derived metrics (intraclass correlation, 0.80 ± 0.07; coefficient of variation, 9% ± 3). Conclusion The proposed four-dimensional (4D) virtual catheter technique enabled reproducible automated evaluation of volumetric intra-aortic hemodynamics alterations from 4D flow MRI in patients with bicuspid aortic valve. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Mitsouras and Hope in this issue.

Intracardiac 4D Flow MRI in Congenital Heart Disease: Recommendations on Behalf of the ISMRM Flow & Motion Study Group.

LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;50:677-681.

Stress increases intracardiac 4D flow cardiovascular magnetic resonance -derived energetics and vorticity and relates to VO2max in Fontan patients.

BACKGROUND: We hypothesize that dobutamine-induced stress impacts intracardiac hemodynamic parameters and that this may be linked to decreased exercise capacity in Fontan patients. Therefore, the purpose of this study was to assess the effect of pharmacologic stress on intraventricular kinetic energy (KE), viscous energy loss (EL) and vorticity from four-dimensional (4D) Flow cardiovascular magnetic resonance (CMR) imaging in Fontan patients and to study the association between stress response and exercise capacity. METHODS: Ten Fontan patients underwent whole-heart 4D flow CMR before and during 7.5 µg/kg/min dobutamine infusion and cardiopulmonary exercise testing (CPET) on the same day. Average ventricular KE, EL and vorticity were computed over systole, diastole and the total cardiac cycle (vorticity_volavg cycle, KEavg cycle, ELavg cycle). The relation to maximum oxygen uptake (VO2 max) from CPET was tested by Pearson's correlation or Spearman's rank correlation in case of non-normality of the data. RESULTS: Dobutamine stress caused a significant 88 ± 52% increase in KE (KEavg cycle: 1.8 ± 0.5 vs 3.3 ± 0.9 mJ, P < 0.001), a significant 108 ± 49% increase in EL (ELavg cycle: 0.9 ± 0.4 vs 1.9 ± 0.9 mW, P < 0.001) and a significant 27 ± 19% increase in vorticity (vorticity_volavg cycle: 3441 ± 899 vs 4394 ± 1322 mL/s, P = 0.002). All rest-stress differences (%) were negatively correlated to VO2 max (KEavg cycle: r = - 0.83, P = 0.003; ELavg cycle: r = - 0.80, P = 0.006; vorticity_volavg cycle: r = - 0.64, P = 0.047). CONCLUSIONS: 4D flow CMR-derived intraventricular kinetic energy, viscous energy loss and vorticity in Fontan patients increase during pharmacologic stress and show a negative correlation with exercise capacity measured by VO2 max.

Disproportionate intraventricular viscous energy loss in Fontan patients: analysis by 4D flow MRI.

AIMS: To non-invasively assess intraventricular viscous energy loss (EL) and proportionality to kinetic energy (KE) in Fontan patients using 4D flow magnetic resonance imaging (MRI) and compare to healthy controls. METHODS AND RESULTS: Thirty Fontan patients and 15 controls underwent 4D flow MRI. Ventricular EL was computed and normalized by end-diastolic volume (EDV). EL over the cardiac cycle (ELcycle) relative to the average kinetic energy (KEcycle) was quantified using a dimensionless index, ELindex (ELcycle/KEcycle). EL was significantly elevated in Fontan patients compared to controls (ELcycle/EDV: 3.7 vs. 2.6 J/m3, P = 0.001). Fontan patients with inflow of blood entering a ventricle, which leaves that ventricle through a ventricular septal defect to the aorta, defined as discordant inflow-to-outflow showed significantly higher EL compared to patients with inflow of blood into the same ventricle from which the blood is ejected into the aorta, defined as concordant inflow-to-outflow (ELcycle/EDV: 6.8 vs. 3.2 J/m3, P = 0.001). EL was not significantly different in Fontan patients with a systemic left vs. a systemic right ventricle (ELcycle/EDV: 3.5 vs. 3.6 J/m3, P = 0.91). ELindex was significantly elevated in Fontan patients compared to controls (ELindex: 0.4 vs. 0.2, P < 0.001). Highest ELindex was found in Fontan patients with discordant inflow-to-outflow compared to concordant inflow-to-outflow (0.5 vs. 0.3, P = 0.01). CONCLUSION: Fontan patients show disproportionate intraventricular EL relative to KE. Intraventricular EL is elevated in these patients compared to healthy controls, and highest EL is found in patients with discordant inflow-to-outflow.