Four-dimensional flow cardiovascular magnetic resonance aortic cross-sectional pressure changes and their associations with flow patterns in health and ascending thoracic aortic aneurysm.

BACKGROUND: Ascending thoracic aortic aneurysm (ATAA) is a silent and threatening dilation of the ascending aorta (AscAo). Maximal aortic diameter which is currently used for ATAA patients management and surgery planning has been shown to inadequately characterize risk of dissection in a large proportion of patients. Our aim was to propose a comprehensive quantitative evaluation of aortic morphology and pressure-flow-wall associations from four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) data in healthy aging and in patients with ATAA. METHODS: We studied 17 ATAA patients (64.7 ± 14.3 years, 5 females) along with 17 age- and sex-matched healthy controls (59.7 ± 13.3 years, 5 females) and 13 younger healthy subjects (33.5 ± 11.1 years, 4 females). All subjects underwent a CMR exam, including 4D flow and three-dimensional anatomical images of the aorta. This latter dataset was used for aortic morphology measurements, including AscAo maximal diameter (iDMAX) and volume, indexed to body surface area. 4D flow MRI data were used to estimate 1) cross-sectional local AscAo spatial (∆PS) and temporal (∆PT) pressure changes as well as the distance (∆DPS) and time duration (∆TPT) between local pressure peaks, 2) AscAo maximal wall shear stress (WSSMAX) at peak systole, and 3) AscAo flow vorticity amplitude (VMAX), duration (VFWHM), and eccentricity (VECC). RESULTS: Consistency of flow and pressure indices was demonstrated through their significant associations with AscAo iDMAX (WSSMAX:r = -0.49, p < 0.001; VECC:r = -0.29, p = 0.045; VFWHM:r = 0.48, p < 0.001; ∆DPS:r = 0.37, p = 0.010; ∆TPT:r = -0.52, p < 0.001) and indexed volume (WSSMAX:r = -0.63, VECC:r = -0.51, VFWHM:r = 0.53, ∆DPS:r = 0.54, ∆TPT:r = -0.63, p < 0.001 for all). Intra-AscAo cross-sectional pressure difference, ∆PS, was significantly and positively associated with both VMAX (r = 0.55, p = 0.002) and WSSMAX (r = 0.59, p < 0.001) in the 30 healthy subjects (48.3 ± 18.0 years). Associations remained significant after adjustment for iDMAX, age, and systolic blood pressure. Superimposition of ATAA patients to normal aging trends between ∆PS and WSSMAX as well as VMAX allowed identifying patients with substantially high pressure differences concomitant with AscAo dilation. CONCLUSION: Local variations in pressures within ascending aortic cross-sections derived from 4D flow MRI were associated with flow changes, as quantified by vorticity, and with stress exerted by blood on the aortic wall, as quantified by wall shear stress. Such flow-wall and pressure interactions might help for the identification of at-risk patients.

Diastolic Function Assessment of Left and Right Ventricles by MRI in Systemic Sclerosis Patients.

BACKGROUND: Heart involvement is frequent although often clinically silent in systemic sclerosis (SSc) patients. Early identification of cardiac involvement can be improved by noninvasive methods such as MRI, in addition to transthoracic echocardiography (TTE). PURPOSE: To assess the ability of phase-contrast (PC)-MRI to detect subclinical left (LV) and right (RV) ventricular diastolic dysfunction in SSc patients. STUDY TYPE: Prospective. POPULATION: Thirty-five consecutive SSc patients (49 ± 14 years) and 35 sex- and age-matched healthy controls (48.6 ± 13.5 years) who underwent TTE and MRI in the same week. FIELD STRENGTH/SEQUENCE: 5 T/PC-MRI using a breath-hold velocity-encoded gradient echo sequence. ASSESSMENT: LV TTE (E/E') and LV and RV PC-MRI indices of diastolic function (LV early and late transmitral [EM , EfM , AM , AfM ] and RV transtricuspid [ET , EfT , AT , AfT ] peak filling flow velocities and flow rates, as well as LV [ E M ' ] and RV [ E T ' ] peak longitudinal myocardial velocities during diastole) were measured. STATISTICAL TESTS: Two-tailed t-test, Wilcoxon test, or Fischer test for comparison of variables between SSc and healthy control groups; sensitivity, specificity, receiver-operating-characteristic (ROC) area under the curve (AUC) to assess discriminative ability of variables. A P-value <0.05 was considered statistically significant. RESULTS: TTE LV E/E' and MRI EM / E M ' and ET / E T ' were significantly higher in SSc patients than in controls (8.27 ± 1.25 vs. 6.70 ± 1.66; 9.43 ± 2.7 vs. 6.51 ± 1.50; 6.51 [4.70-10.40] vs. 4.13 [3.22-5.75], respectively) and separated SSc patients and healthy controls with good sensitivity (68%, 71%, and 80%), specificity (85%, 94%, and 62%), and AUC (0.787, 0.807, and 0.765). LV EfM was significantly higher in SSc patients than in controls (347.1 ± 113.7 vs. 284.7 ± 94.6) as RVAfT (277 [231-355] vs. 220 [154-253] mL/sec) with impaired relaxation pattern (EfT /AfT , 0.95 [0.87-1.21] vs. 1.12 [0.93-1.47]). DATA CONCLUSION: MRI was able to detect LV and RV diastolic dysfunction in SSc patients with good accuracy in the absence of LV systolic dysfunction at echocardiography. Use of MRI can allow to better assess the early impact of myocardial fibrosis related to SSc. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Deep Learning-based Automated Aortic Area and Distensibility Assessment: the Multi-Ethnic Study of Atherosclerosis (MESA).

This study details application of deep learning for automatic segmentation of the ascending and descending aorta from 2D phase-contrast cine magnetic resonance imaging for automatic aortic analysis on the large MESA cohort with assessment on an external cohort of thoracic aortic aneurysm (TAA) patients. This study includes images and corresponding analysis of the ascending and descending aorta at the pulmonary artery bifurcation from the MESA study. Train, validation, and internal test sets consisted of 1123 studies (24,282 images), 374 studies (8067 images), and 375 studies (8069 images), respectively. The external test set of TAAs consisted of 37 studies (3224 images). CNN performance was evaluated utilizing a dice coefficient and concordance correlation coefficients (CCC) of geometric parameters. Dice coefficients were as high as 97.55% (CI: 97.47-97.62%) and 93.56% (CI: 84.63-96.68%) on the internal and external test of TAAs, respectively. CCC for maximum and minimum and ascending aortic area were 0.969 and 0.950, respectively, on the internal test set and 0.997 and 0.995, respectively, for the external test. The absolute differences between manual and deep learning segmentations for ascending and descending aortic distensibility were 0.0194 × 10-4 ± 9.67 × 10-4 and 0.002 ± 0.001 mmHg-1, respectively, on the internal test set and 0.44 × 10-4 ± 20.4 × 10-4 and 0.002 ± 0.001 mmHg-1, respectively, on the external test set. We successfully developed a U-Net-based aortic segmentation and analysis algorithm in both MESA and in external cases of TAA.

Impact of sequence type and field strength (1.5, 3, and 7T) on 4D flow MRI hemodynamic aortic parameters in healthy volunteers.

PURPOSE: 4D flow magnetic resonance imaging (4D-MRI) allows time-resolved visualization of blood flow patterns, quantification of volumes, velocities, and advanced parameters, such as wall shear stress (WSS). As 4D-MRI enters the clinical arena, standardization and awareness of confounders are important. Our aim was to evaluate the equivalence of 4D flow-derived aortic hemodynamics in healthy volunteers using different sequences and field strengths. METHODS: 4D-MRI was acquired in 10 healthy volunteers at 1.5T using three different prototype sequences, at 3T and at 7T (Siemens Healthineers). After evaluation of diagnostic quality in three segments (ascending-, descending aorta, aortic arch), peak velocity, flow volumes, and WSS were investigated. Equivalence limits for comparison of field strengths/sequences were based on the limits of Bland-Altman analyses of the intraobserver variability. RESULTS: Non-diagnostic quality was found in 10/144 segments, 9/10 were obtained at 7T. Apart for the comparison of forward flow between sequence 1 and 3, the differences in measurements between field strengths/sequences exceeded the range of agreement. Significant differences were found between field strengths/sequences for forward flow (1.5T vs. 3T, 3T vs. 7T, sequence 1 vs. 3, 2 vs. 3 [P < .001]), WSS (1.5T vs. 3T [P < .05], sequence 1 vs. 2, 1 vs. 3, 2 vs. 3 [P < .001]), and peak velocity (1.5T vs. 7T, sequence 1 vs. 3 [P > .001]). All parameters at all field strengths/with all sequences correlated moderately to strongly (r ≥ 0.5). CONCLUSION: Data from all sequences could be acquired and resulting images showed sufficient quality for further analysis. However, the variability of the measurements of peak velocity, flow volumes, and WSS was higher when comparing field strengths/sequences as the equivalence limits defined by the intraobserver assessments.

Effect of Aortic Valve Disease on 3D Hemodynamics in Patients With Aortic Dilation and Trileaflet Aortic Valve Morphology.

BACKGROUND: The effect of different expressions of aortic valve disease on 3D aortic hemodynamics is unclear. PURPOSE: To investigate changes in aortic hemodynamics in patients with dilated ascending aorta (AAo) but different severity of aortic valve stenosis (AS) and/or regurgitation (AR). STUDY TYPE: Retrospective. POPULATION: A total of 111 subjects (86 patients with AAo diameter ≥ 40 mm and 25 healthy controls, all with trileaflet aortic valve [TAV]). Patients were further stratified by TAV dysfunction: n = 9 with combined moderate or severe AS and AR (ASR, 56 ± 13 years), n = 14 with moderate or severe AS (AS, 64 ± 14 years), n = 33 with moderate or severe AR (AR, 62 ± 14 years), n = 30 with neither AS nor AR (no AS/AR, 63 ± 9 years). FIELD STRENGTH/SEQUENCE: 4D flow MRI on 1.5/3T systems for the in vivo analysis of aortic blood flow dynamics. ASSESSMENT: Data analysis included grading of 3D AAo vortex/helix flow and AAo flow eccentricity as well as quantification of systolic peak velocities and wall shear stress (WSS). STATISTICAL TESTS: Continuous variables were compared by one-way analysis of variance or Kruskal-Wallis, followed by a pairwise Tukey or Dunn test if there was a significant difference. RESULTS: All patients demonstrated markedly elevated vortex and helix flow compared with controls (P < 0.05). Peak velocities were significantly elevated in ASR, AS, and AR patients compared with controls (P < 0.05). Increased flow eccentricity was observed in entire AAo for AR, at the mid and distal AAo for ASR and AS, and at the proximal AAo for no AS/AR. Compared with controls, WSS in the AAo was significantly elevated in ASR and AS patients (P < 0.05) and reduced in no AS/AR patients (P < 0.05). DATA CONCLUSION: The presence of TAV dysfunction is associated with aberrant hemodynamics and altered WSS, which may play a role in the development of aortopathy. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:481-491.

Left ventricular and proximal aorta coupling in magnetic resonance imaging: aging together?

The importance of aorta-ventricular coupling in cardiovascular disease is recognized but underestimated. The contribution of the age-related decline in ascending aortic function compared with characteristic impedance and total peripheral resistance on left ventricular function and remodeling is poorly studied. Our aim was to evaluate the relation of proximal aortic distensibility and impedance with left ventricular geometry and function in asymptomatic individuals. We prospectively studied 100 subjects (47 men, 53 women, age: 20-84 yr). Aortic strain, distensibility, arch pulse wave velocity, characteristic impedance (Zc), total peripheral resistance, left ventricular (LV) volumes and mass, wall stress, and peak global circumferential myocardial strain and strain rates were determined by MRI. Central pressures were measured from tonometry. Ea/Ev, an index of vascular-ventricular coupling, and LV wall stress were preserved across age- or aortic-stiffness-stratified groups. Static and pulsatile components of aortic load were differentially associated with age. Increased total vascular resistance was associated with decreased LV strain and increased concentric remodeling [ratio of LV mass to end-diastolic volume (M/V ratio)] in all individuals. In younger individuals (<45 yr), aortic distensibility was related to LV strain and concentric remodeling (M/V ratio), whereas Zc was related to LV strain and concentric remodeling (M/V ratio) in older individuals (>45 yr). Early age-related stiffening of the ascending aorta is a component of LV afterload subsequently associated with increased aortic impedance and alterations in LV geometry, namely concentric remodeling, decreased myocardial strain, and increased stroke work such that LV wall stress and arterial-ventricular coupling are preserved. NEW & NOTEWORTHY Local flow and deformation can both be assessed with high precision noninvasively in the ascending aorta using MRI. Combined with central pressure measurement, they provide distensibility and impedance and simultaneous reference assessment of left ventricular deformation and geometry, hence a comprehensive evaluation of arterial-ventricular coupling to study physiology and disease.

Analysis of aortic pressure fields from 4D flow MRI in healthy volunteers: Associations with age and left ventricular remodeling.

BACKGROUND: Aging-related arterial stiffness is associated with substantial changes in global and local arterial pressures. The subsequent early return of reflected pressure waves leads to an elevated left ventricular (LV) afterload and ultimately to a deleterious concentric LV remodeling. PURPOSE: To compute aortic time-resolved pressure fields of healthy subjects from 4D flow MRI and to define relevant pressure-based markers while investigating their relationship with age, LV remodeling, as well as tonometric augmentation index (AIx) and pulse wave velocity (PWV). STUDY TYPE: Retrospective. POPULATION: Forty-seven healthy subjects (age: 49.5 ± 18 years, 24 women). FIELD STRENGTH/SEQUENCE: 3 T/4D flow MRI. ASSESSMENT: Spatiotemporal pressure fields were computed by integrating velocity-derived pressure gradients using Navier-Stokes equations, while assuming zero pressure at the sino-tubular junction. To quantify aortic pressure spatiotemporal variations, we defined the following markers: 1) volumetric aortic pressure propagation rates ΔP E1 /ΔV and ΔP E2 /ΔV, representing variations of early and late systolic relative pressure peaks along the aorta, respectively, according to the cumulated aortic volume; 2) ΔA PE1-PE2 defined in four aortic regions as the absolute difference between early and late systolic relative pressure peaks amplitude. STATISTICAL TESTS: Linear regression, Wilcoxon rank sum test, Bland-Altman analysis, and intraclass correlation coefficients (ICC). RESULTS: Spatiotemporal variations of aortic pressure peaks were moderately to highly reproducible (ICC ≥0.50) and decreased significantly with age, in terms of absolute magnitude: ΔP E1 /ΔV (r = 0.70, P < 0.005), ΔP E2 /ΔV (r = -0.45, P < 0.005) and ΔA PE1-PE2 (|r| > 0.39, P < 0.005). ΔP E1 /ΔV was associated with LV remodeling (r = 0.53, P < 0.001) and ascending aorta ΔA PE1-PE2 was associated with AIx (r = -0.59, P < 0.001). Both associations were independent of age and systolic blood pressures. Only weak associations were found between pressure indices and PWV (r ≤ 0.40). DATA CONCLUSION: 4D flow MRI relative aortic pressures were consistent with physiological knowledge as demonstrated by their significant volumetric and temporal variations with age and their independent association with LV remodeling and augmentation index. Level of Evidence 2 Technical Efficacy Stage 3 J. Magn. Reson. Imaging 2019;50:982-993.

Comparison of different methods for the estimation of aortic pulse wave velocity from 4D flow cardiovascular magnetic resonance.

BACKGROUND: Arterial pulse wave velocity (PWV) is associated with increased mortality in aging and disease. Several studies have shown the accuracy of applanation tonometry carotid-femoral PWV (Cf-PWV) and the relevance of evaluating central aorta stiffness using 2D cardiovascular magnetic resonance (CMR) to estimate PWV, and aortic distensibility-derived PWV through the theoretical Bramwell-Hill model (BH-PWV). Our aim was to compare various methods of aortic PWV (aoPWV) estimation from 4D flow CMR, in terms of associations with age, Cf-PWV, BH-PWV and left ventricular (LV) mass-to-volume ratio while evaluating inter-observer reproducibility and robustness to temporal resolution. METHODS: We studied 47 healthy subjects (49.5 ± 18 years) who underwent Cf-PWV and CMR including aortic 4D flow CMR as well as 2D cine SSFP for BH-PWV and LV mass-to-volume ratio estimation. The aorta was semi-automatically segmented from 4D flow data, and mean velocity waveforms were estimated in 25 planes perpendicular to the aortic centerline. 4D flow CMR aoPWV was calculated: using velocity curves at two locations, namely ascending aorta (AAo) and distal descending aorta (DAo) aorta (S1, 2D-like strategy), or using all velocity curves along the entire aortic centreline (3D-like strategies) with iterative transit time (TT) estimates (S2) or a plane fitting of velocity curves systolic upslope (S3). For S1 and S2, TT was calculated using three approaches: cross-correlation (TTc), wavelets (TTw) and Fourier transforms (TTf). Intra-class correlation coefficients (ICC) and Bland-Altman biases (BA) were used to evaluate inter-observer reproducibility and effect of lower temporal resolution. RESULTS: 4D flow CMR aoPWV estimates were significantly (p < 0.05) correlated to the CMR-independent Cf-PWV, BH-PWV, age and LV mass-to-volume ratio, with the strongest correlations for the 3D-like strategy using wavelets TT (S2-TTw) (R = 0.62, 0.65, 0.77 and 0.52, respectively, all p < 0.001). S2-TTw was also highly reproducible (ICC = 0.99, BA = 0.09 m/s) and robust to lower temporal resolution (ICC = 0.97, BA = 0.15 m/s). CONCLUSIONS: Reproducible 4D flow CMR aoPWV estimates can be obtained using full 3D aortic coverage. Such 4D flow CMR stiffness measures were significantly associated with Cf-PWV, BH-PWV, age and LV mass-to-volume ratio, with a slight superiority of the 3D strategy using wavelets transit time (S2-TTw).

4-D flow MRI aortic 3-D hemodynamics and wall shear stress remain stable over short-term follow-up in pediatric and young adult patients with bicuspid aortic valve.

BACKGROUND: Children with bicuspid aortic valve (BAV) are at risk for serious complications including aortic valve stenosis and aortic rupture. Most studies investigating biomarkers predictive of BAV complications are focused on adults. OBJECTIVE: To investigate whether hemodynamic parameters change over time in children and young adults with BAV by comparing baseline and follow-up four-dimensional (4-D) flow MRI examinations. MATERIALS AND METHODS: We retrospectively included 19 children and young adults with BAV who had serial 4-D flow MRI exams (mean difference in scan dates 1.8±1.0 [range, 0.6-3.4 years]). We compared aortic peak blood flow velocity, three-dimensional (3-D) wall shear stress, aortic root and ascending aortic (AAo) z-scores between baseline and follow-up exams. We generated systolic streamlines for all patients and visually compared their baseline and follow-up exams. RESULTS: The only significant difference between baseline and follow-up exams occurred in AAo z-scores (3.12±2.62 vs. 3.59±2.76, P<0.05) indicating growth of the AAo out of proportion to somatic growth. There were no significant changes in either peak velocity or 3-D wall shear stress between baseline and follow-up exams. Ascending aortic peak velocity at baseline correlated with annual change in AAo z-score (r=0.58, P=0.009). Visual assessment revealed abnormal blood flow patterns, which were unique to each patient and remained stable between baseline and follow-up exams. CONCLUSION: In our pediatric and young adult BAV cohort, hemodynamic markers and systolic blood flow patterns remained stable over short-term follow-up despite significant AAo growth, suggesting minimal acute disease progression. Baseline AAo peak velocity was a predictor of AAo dilation and might help in determining pediatric patients with BAV who are at risk of increased AAo growth.

k-t accelerated aortic 4D flow MRI in under two minutes: Feasibility and impact of resolution, k-space sampling patterns, and respiratory navigator gating on hemodynamic measurements.

PURPOSE: To assess the performance of highly accelerated free-breathing aortic four-dimensional (4D) flow MRI acquired in under 2 minutes compared to conventional respiratory gated 4D flow. METHODS: Eight k-t accelerated nongated 4D flow MRI (parallel MRI with extended and averaged generalized autocalibrating partially parallel acquisition kernels [PEAK GRAPPA], R = 5, TRes = 67.2 ms) using four ky -kz Cartesian sampling patterns (linear, center-out, out-center-out, random) and two spatial resolutions (SRes1 = 3.5 × 2.3 × 2.6 mm3 , SRes2 = 4.5 × 2.3 × 2.6 mm3 ) were compared in vitro (aortic coarctation flow phantom) and in 10 healthy volunteers, to conventional 4D flow (16 mm-navigator acceptance window; R = 2; TRes = 39.2 ms; SRes = 3.2 × 2.3 × 2.4 mm3 ). The best k-t accelerated approach was further assessed in 10 patients with aortic disease. RESULTS: The k-t accelerated in vitro aortic peak flow (Qmax), net flow (Qnet), and peak velocity (Vmax) were lower than conventional 4D flow indices by ≤4.7%, ≤ 11%, and ≤22%, respectively. In vivo k-t accelerated acquisitions were significantly shorter but showed a trend to lower image quality compared to conventional 4D flow. Hemodynamic indices for linear and out-center-out k-space samplings were in agreement with conventional 4D flow (Qmax ≤ 13%, Qnet ≤ 13%, Vmax ≤ 17%, P > 0.05). CONCLUSION: Aortic 4D flow MRI in under 2 minutes is feasible with moderate underestimation of flow indices. Differences in k-space sampling patterns suggest an opportunity to mitigate image artifacts by an optimal trade-off between scan time, acceleration, and k-space sampling. Magn Reson Med 79:195-207, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Distribution of blood flow velocity in the normal aorta: Effect of age and gender.

PURPOSE: To apply flow distribution analysis in the entire aorta across a wide age range from pediatric to adult subjects. MATERIAL AND METHODS: In all, 98 healthy subjects (age 9-78 years, 41 women) underwent 4D flow MRI at 1.5T and 3T for the assessment of 3D blood flow in the thoracic aorta. Subjects were categorized into age groups: group 1 (n = 9, 5 women): 9-15 years; group 2 (n = 13, 8 women): 16-20 years; group 3 (n = 27, 14 women): 21-39 years; group 4 (n = 40, 11 women): 40-59 years; group 5 (n = 9, 3 women): >60 years. Data analysis included the 3D segmentation of the aorta, aortic valve peak velocity, mid-ascending aortic diameter, and calculation of flow velocity distribution descriptors (mean, median, standard deviation, incidence of velocities >1 m/s, skewness, and kurtosis of aortic velocity magnitude). Ascending aortic diameter was normalized by body surface area. RESULTS: Age was significantly associated with normalized aortic diameter (R = 0.73, P < 0.001), skewness (R = 0.76, P < 0.001), and kurtosis (R = 0.74, P < 0.001), all adjusted by heart rate. Aortic peak velocity and velocity distribution descriptors, adjusted by heart rate, were significantly different between age groups (P < 0.001, analysis of covariance). Skewness and kurtosis significantly increased (P < 0.001) during adulthood (>40 years) as compared with childhood (<21 years). Men and women revealed significant differences (P ≤ 0.05) for peak velocity, incidence, mean, median, standard deviation, and skewness, all adjusted by heart rate. CONCLUSION: Aortic hemodynamics significantly change with age and gender, indicating the importance of age- and gender-matched control cohorts for the assessment of the impact of cardiovascular disease on aortic blood flow. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;47:487-498.

New estimate of valvuloarterial impedance in aortic valve stenosis: A cardiac magnetic resonance study.

PURPOSE: Valvuloarterial impedance (ZVA ), estimating left ventricle (LV) afterload, has been proposed in transthoracic echocardiography (TTE) as a predictor of mortality in aortic valve stenosis (AVS). However, its calculation differs from arterial characteristic impedance (ZC ). Our aim was to apply the concept of ZC calculation to estimate ZVA from MR with carotid tonometry and to evaluate these indices through their associations with symptoms, LV diastolic function and aortic stiffness. MATERIALS AND METHODS: In 40 patients with AVS (76 ± 13 years), ZVA-TI derived from velocity time integral and E/Ea were estimated by TTE. ZVA-INS , based on ZC formula, calculated as the instantaneous pressure gradient to peak flow ratio and aortic compliance were estimated by using MRI at 1.5 Tesla. RESULTS: Both ZVA estimates were higher in symptomatic than asymptomatic patients (707 ± 22 versus 579 ± 53 dyne.s/cm5 , P = 0.031 for ZVA-INS and 4.35 ± 0.16 versus 3.33 ± 0.38 mmHg.m2 /mL, P = 0.018 for ZVA-TI ). Although they were both associated with aortic compliance (r = -0.45; P = 0.006 for ZVA-INS and r = -0.43; P = 0.008 for ZVA-TI ) only ZVA-INS was associated with E/Ea (r = 0.50; P < 0.001). In multivariate analysis to identify determinants of E/Ea, a model including age, mean blood pressure, LV ejection fraction, LV mass, and aortic valve area was performed (R2 = 0.41; P < 0.01). When ZVA-INS was added to the model, its overall significance was higher R2 = 0.56 (P < 0.01) and ZVA-INS and LV mass were the only significant determinants. CONCLUSION: ZVA-INS was more strongly associated with diastolic dysfunction than usual parameters quantifying AVS severity. This new ZVA estimate could improve LV afterload evaluation. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:795-803.

Longitudinal Evaluation of Aortic Hemodynamics in Marfan Syndrome: New Insights from a 4D Flow Cardiovascular Magnetic Resonance Multi-Year Follow-Up Study.

BACKGROUND: The aim of this 4D flow cardiovascular magnetic resonance (CMR) follow-up study was to investigate longitudinal changes in aortic hemodynamics in adolescent patients with Marfan syndrome (MFS). METHODS: 4D flow CMR for the assessment of in-vivo 3D blood flow with full coverage of the thoracic aorta was performed twice (baseline scan t1/follow-up scan t2) in 19 adolescent MFS patients (age at t1: 12.7 ± 3.6 years, t2: 16.2 ± 4.3 years) with a mean follow-up duration of 3.5 ± 1.2 years. Ten healthy volunteers (24 ± 3.8 years) served as a control group. Data analysis included aortic blood flow visualization by color-coded 3D pathlines, and grading of flow patterns (helices/vortices) on a 3-point scale (none, moderate, severe; blinded reading, 2 observers). Regional aortic peak systolic velocities and systolic 3D wall shear stress (WSS) along the entire aortic wall were quantified. Z-Scores of the aortic root and proximal descending aorta (DAo) were assessed. RESULTS: Regional systolic WSS was stable over the follow-up duration, except for a significant decrease in the proximal inner DAo segment (p = 0.02) between t1 and t2. MFS patients revealed significant lower mean systolic WSS in the proximal inner DAo compared with volunteers (0.78 ± 0.15 N/m2) at baseline t1 (0.60 ± 0.18 N/m2; p = 0.01) and follow-up t2 (0.55 ± 0.16 N/m2; p = 0.001). There were significant relationships (p < 0.01) between the segmental WSS in the proximal inner DAo, DAo Z-scores (r = -0.64) and helix/vortex pattern grading (r = -0.55) at both t1 and t2. The interobserver agreement for secondary flow patterns assessment was excellent (Cohen's k = 0.71). CONCLUSIONS: MFS patients have lower segmental WSS in the inner proximal DAo segment which correlates with increased localized aberrant vortex/helix flow patterns and an enlarged diameter at one of the most critical sites for aortic dissection. General aortic hemodynamics are stable but these subtle localized DAo changes are already present at young age and tend to be more pronounced in the course of time.

Altered aortic 3D hemodynamics and geometry in pediatric Marfan syndrome patients.

BACKGROUND: Blood flow dynamics make it possible to better understand the development of aortopathy and cardiovascular events in patients with Marfan syndrome (MFS). Aortic 3D blood flow characteristics were investigated in relation to aortic geometry in children and adolescents with MFS. METHODS: Twenty-five MFS patients (age 15.6 ± 4.0 years; 11 females) and 21 healthy controls (age 16.0 ± 2.6 years; 12 females) underwent magnetic resonance angiography and 4D flow CMR for assessment of thoracic aortic size and 3D blood flow velocities. Data analysis included calculation of aortic diameter and BSA-indexed aortic dimensions (Z-score) along the thoracic aorta, 3D mean systolic wall shear stress (WSSmean) in ten aortic segments and assessment of aortic blood flow patterns. RESULTS: Aortic root (root), ascending (AAo) and descending (DAo) aortic size was significantly larger in MFS patients than healthy controls (Root Z-score: 3.56 ± 1.45 vs 0.49 ± 0.78, p < 0.001; AAo Z-score 0.21 ± 0.95 vs -0.54 ± 0.64, p = 0.004; proximal DAo Z-score 2.02 ± 1.60 vs 0.56 ± 0.66, p < 0.001). A regional variation in prevalence and severity of flow patterns (vortex and helix flow patterns) was observed, with the aortic root and the proximal DAo (pDAo) being more frequently affected in MFS. MFS patients had significantly reduced WSSmean in the proximal AAo (pAAo) outer segment (0.65 ± 0.12 vs. 0.73 ± 0.14 Pa, p = 0.029) and pDAo inner segment (0.74 ± 0.17 vs. 0.87 ± 0.21 Pa, p = 0.021), as well as higher WSSmean in the inner segment of the distal AAo (0.94 ± 0.14 vs. 0.84 ± 0.15 Pa, p = 0.036) compared to healthy subjects. An inverse relationship existed between pDAo WSSmean and both pDAo diameter (R = -0.53, p < 0.001) and % diameter change along the pDAo segment (R = -0.64, p < 0.001). CONCLUSIONS: MFS children and young adults have altered aortic flow patterns and differences in aortic WSS that were most pronounced in the pAAo and pDAo, segments where aortic dissection or rupture often originate. The presence of vortex flow patterns and abnormal WSS correlated with regional size of the pDAo and are potentially valuable additional markers of disease severity.

MR and applanation tonometry derived aortic impedance: association with aging and left ventricular remodeling.

PURPOSE: We sought to noninvasively estimate aortic impedance indices from MR and tonometric data. MATERIALS AND METHODS: MR aortic velocity-encoded and carotid applanation tonometry pressure data of 70 healthy subjects (19-79 years) were used to calculate the following indices from impedance spectrum: (i) characteristic impedance (Zc) reflecting pulsatile component of left ventricular (LV) afterload, (ii) frequency of the minimal impedance magnitude related to arterial compliance (FMIN ), (iii) total peripheral resistance (TPR) related to steady LV load, (iv) impedance oscillatory index (ZINDEX ) related to proximal reflections, and (v) reflection magnitude (RM). Associations with age and LV remodeling (LV mass/end-diastolic volume) were investigated using multivariate analysis. RESULTS: All indices except Zc were associated with age independent of subjects characteristics and systolic blood pressures. They were all significantly associated with the well-established carotid-femoral pulse wave velocity (r ≥ 0.29; P < 0.01). However, such associations were not independent of age. Pulsatile index Zc was independently associated with carotid pulse pressure (r = 0.53, P < 0.001). Moreover, conversely to conventional stiffness indices, Zc and TPR were independently associated with LV remodeling (r = 0.30, r = 0.43, respectively, P < 0.01). CONCLUSION: We estimated aortic impedance from velocity-encoded MR and tonometry data resulting in reliable impedance and reflection indices as confirmed by their significant and independent associations with age and LV remodeling.

Age-specific changes in left ventricular diastolic function: a velocity-encoded magnetic resonance imaging study.

OBJECTIVES: Our objectives were to assess the ability of phasecontrast MRI (PC-MRI) to detect sub-clinical age-related variations of left ventricular (LV) diastolic parameters and thus to provide age-related reference ranges currently available for echocardiography but not for MRI-PC, and to identify independent associates of such variations. METHODS: We studied 100 healthy volunteers (age = 42 ± 15years, 50 females) who had MRI with simultaneous blood pressure measurements. LV mass and volumes were assessed. Semiautomated analysis of PC-MRI data provided: 1) early transmitral (Ef) and atrial (Af) peak filling flow-rates (ml/s) and filling volume (FV), 2) deceleration time (DT), isovolumic relaxation time (IVRT), and 3) early myocardial longitudinal (E') peak velocity. RESULTS: MRI-PC diastolic parameters were reproducible as reflected by low coefficients of variations (ranged between 0.31 to 6.26 %). Peak myocardial velocity E' (r = -0.63, p < 0.0001) and flow-rate parameters were strongly and independently associated to age (Ef/Af:r = -0.63, DT:r = 0.46, IVRT:r = 0.44, Ef/FV:r = -0.55, Af/FV:r = 0.56, p < 0.0001). Furthermore, LV relaxation parameters (E', DT, IVRT), were independently associated to LV remodelling (LV mass/end-diastolic volume) and myocardial wall thickness (p < 0.01). CONCLUSIONS: PC-MRI age-related reference ranges of diastolic parameters are provided. Such parameters might be useful for a fast, reproducible and reliable characterization of diastolic function in patients referred for clinical MRI exam KEY POINTS: • MRI age-related reference values of left ventricular diastolic parameters are provided. • MRI diastolic parameters can characterise sub-clinical age-related variations in healthy individuals. • Diastolic function would complement cardiac MRI exam with currently neglected data. • Diastolic function would enhance MRI diagnostic value in cardiomyopathy and heartfailure.

Estimation of aortic pulse wave transit time in cardiovascular magnetic resonance using complex wavelet cross-spectrum analysis.

BACKGROUND: Aortic pulse wave velocity (PWV), which substantially increases with arterial stiffness and aging, is a major predictor of cardiovascular mortality. It is commonly estimated using applanation tonometry at carotid and femoral arterial sites (cfPWV). More recently, several cardiovascular magnetic resonance (CMR) studies have focused on the measurement of aortic arch PWV (archPWV). Although the excellent anatomical coverage of CMR offers reliable segmental measurement of arterial length, accurate transit time (TT) determination remains a challenge. Recently, it has been demonstrated that Fourier-based methods were more robust to low temporal resolution than time-based approaches. METHODS: We developed a wavelet-based method, which enables temporal localization of signal frequencies, to estimate TT from ascending and descending aortic CMR flow curves. This method (archPWVWU) combines the robustness of Fourier-based methods to low temporal resolution with the possibility to restrict the analysis to the reflectionless systolic upslope. We compared this method with Fourier-based (archPWVF) and time domain upslope (archPWVTU) methods in relation to linear correlations with age, cfPWV and effects of decreasing temporal resolution by factors of 2, 3 and 4. We studied 71 healthy subjects (45 ± 15 years, 29 females) who underwent CMR velocity acquisitions and cfPWV measurements. RESULTS: Comparison with age resulted in the highest correlation for the wavelet-based method (archPWVWU:r = 0.84,p < 0.001; archPWVTU:r = 0.74,p < 0.001; archPWVF:r = 0.63,p < 0.001). Associations with cfPWV resulted in the highest correlations for upslope techniques whether based on wavelet (archPWVWU:r = 0.58,p < 0.001) or time (archPWVTU:r = 0.58,p < 0.001) approach. Furthermore, while decreasing temporal resolution by 4-fold induced only a minor decrease in correlation of both archPWVWU (r decreased from 0.84 to 0.80) and archPWVF (r decreased from 0.63 to 0.51) with age, it induced a major decrease for the archPWVTU age relationship (r decreased from 0.74 to 0.38). CONCLUSIONS: By CMR, measurement of aortic arch flow TT using systolic upslopes resulted in a better correlation with age and cfPWV, as compared to the Fourier-based approach applied on the entire cardiac cycle. Furthermore, methods based on harmonic decomposition were less affected by low temporal resolution. Since the proposed wavelet approach combines these two advantages, it might help to overcome current technical limitations related to CMR temporal resolution and evaluation of patients with highly stiff arteries.

Geometry is a major determinant of flow reversal in proximal aorta.

The aim of this study is to quantify aortic backward flow (BF) using phase-contrast cardiovascular magnetic resonance (PC-CMR) and to study its associations with age, indexes of arterial stiffness, and geometry. Although PC-CMR blood flow studies showed a simultaneous presence of BF and forward flow (FF) in the ascending aorta (AA), the relationship between aortic flows and aging as well as arterial stiffness and geometry in healthy volunteers has never been reported. We studied 96 healthy subjects [47 women, 39 ± 15 yr old (19-79 yr)]. Aortic stiffness [arch pulse wave velocity (PWVAO), AA distensibility], geometry (AA diameter and arch length), and parameters related to AA BF and FF (volumes, peaks, and onset times) were estimated from CMR. Applanation tonometry carotid-femoral pulse-wave velocity (PWVCF), carotid augmentation index, and time to return of the reflected pressure wave were assessed. Whereas FF parameters remained unchanged, BF onset time shortened significantly (R(2) = 0.18, P < 0.0001) and BF volume and BF-to-FF peaks ratio increased significantly (R(2) = 0.38 and R(2) = 0.44, respectively, P < 0.0001) with aging. These two latter BF indexes were also related to stiffness indexes (PWVCF, R(2) > 0.30; PWVAO, R(2) > 0.24; and distensibility, R(2) > 0.20, P < 0.001), augmentation index (R(2) > 0.20, P < 0.001), and aortic geometry (AA diameter, R(2) > 0.58; and arch length, R(2) > 0.31, P < 0.001). In multivariate analysis, aortic diameter was the strongest independent correlate of BF beyond age effect. In conclusion, AA BF estimated using PC-CMR increased significantly in terms of magnitude and volume and appeared earlier with aging and was mostly determined by aortic geometry. Thus BF indexes could be relevant markers of subclinical arterial wall alterations.

Changes of aortic hemodynamics after aortic valve replacement-A four dimensional flow cardiovascular magnetic resonance follow up study.

Objectives: Non-invasive assessment of aortic hemodynamics using four dimensional (4D) flow magnetic resonance imaging (MRI) provides new information on blood flow patterns and wall shear stress (WSS). Aortic valve stenosis (AS) and/or bicuspid aortic valves (BAV) are associated with altered aortic flow patterns and elevated WSS. Aim of this study was to investigate changes in aortic hemodynamics over time in patients with AS and/or BAV with or without aortic valve replacement. Methods: We rescheduled 20 patients for a second 4D flow MRI examination, whose first examination was at least 3 years prior. A total of 7 patients received an aortic valve replacement between baseline and follow up examination (=operated group = OP group). Aortic flow patterns (helicity/vorticity) were assessed using a semi-quantitative grading approach from 0 to 3, flow volumes were evaluated in 9 planes, WSS in 18 and peak velocity in 3 areas. Results: While most patients had vortical and/or helical flow formations within the aorta, there was no significant change over time. Ascending aortic forward flow volumes were significantly lower in the OP group than in the NOP group at baseline (NOP 69.3 mL ± 14.2 mL vs. OP 55.3 mL ± 1.9 mL p = 0.029). WSS in the outer ascending aorta was significantly higher in the OP group than in the NOP group at baseline (NOP 0.6 ± 0.2 N/m2 vs. OP 0.8 ± 0.2 N/m2, p = 0.008). Peak velocity decreased from baseline to follow up in the aortic arch only in the OP group (1.6 ± 0.6 m/s vs. 1.2 ± 0.3 m/s, p = 0.018). Conclusion: Aortic valve replacement influences aortic hemodynamics. The parameters improve after surgery.

Associations of aortic stiffness and intra-aortic flow parameters with epicardial adipose tissue in patients with type-2 diabetes.

Background: It has been shown that increased aortic stiffness is related to type-2 diabetes (T2D) which is considered as a risk factor for cardiovascular disease. Among other risk factors is epicardial adipose tissue (EAT) which is increased in T2D and is a relevant biomarker of metabolic severity and adverse outcome. Purpose: To assess aortic flow parameters in T2D patients as compared to healthy individuals and to evaluate their associations with EAT accumulation as an index of cardiometabolic severity in T2D patients. Materials and methods: Thirty-six T2D patients as well as 29 healthy controls matched by age and sex were included in this study. Participants had cardiac and aortic MRI exams at 1.5 T. Imaging sequences included cine SSFP for left ventricle (LV) function and EAT assessment and aortic cine and phase-contrast imaging for strain and flow parameters quantification. Results: In this study, we found LV phenotype to be characterized by concentric remodeling with decreased stroke volume index despite global LV mass within a normal range. EAT was increased in T2D patients compared to controls (p<0.0001). Moreover, EAT, a biomarker of metabolic severity, was negatively correlated to ascending aortic (AA) distensibility (p=0.048) and positively to the normalized backward flow volume (p=0.001). These relationships remained significant after further adjustment for age, sex and central mean blood pressure. In a multivariate model, presence/absence of T2D and AA normalized backward flow (BF) to forward flow (FF) volumes ratio are both significant and independent correlates of EAT. Conclusion: In our study, aortic stiffness as depicted by an increased backward flow volume and decreased distensibility seems to be related to EAT volume in T2D patients. This observation should be confirmed in the future on a larger population while considering additional biomarkers specific to inflammation and using a longitudinal prospective study design.