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.

Magnetic resonance imaging 4-D flow-based analysis of aortic hemodynamics in Turner syndrome.

BACKGROUND: Cardiovascular surveillance is important in Turner syndrome because of the increased risk of aortic dilation and dissection with consecutively increased mortality. OBJECTIVE: To compare 4-D flow MRI for the characterization of aortic 3-D flow patterns, dimensions and vessel wall parameters in pediatric patients with Turner syndrome and age-matched controls. MATERIALS AND METHODS: We performed 4-D flow MRI measuring in vivo 3-D blood flow with coverage of the thoracic aorta in 25 patients with Turner syndrome and in 16 female healthy controls (age mean ± standard deviation were 16 ± 5 years and 17 ± 4 years, respectively). Blood flow was visualized by time-resolved 3-D path lines. Visual grading of aortic flow in terms of helices and vortices was performed by two independent observers. Quantitative analysis included measurement of aortic diameters, quantification of peak systolic wall shear stress, pulsatility index and oscillatory shear index at eight defined sites. RESULTS: Patients with Turner syndrome had significantly larger aortic diameters normalized to BSA, increased vortices in the ascending aorta and elevated helix flow in the ascending and descending aorta compared to controls (all P<0.03). Patients with abnormal helical or vortical flow in the ascending aorta had significantly larger diameters of the ascending aorta (P<0.03). Peak systolic wall shear stress, pulsatility index and oscillatory shear index were significantly lower in Turner patients compared to controls (p=0.02, p=0.002 and p=0.01 respectively). CONCLUSION: Four-dimensional flow MRI provides new insights into the altered aortic hemodynamics and wall shear stress that could have an impact on the development of aortic dissections.

Assessment of intracardiac flow and vorticity in the right heart of patients after repair of tetralogy of Fallot by flow-sensitive 4D MRI.

OBJECTIVES: To comprehensively and quantitatively analyse flow and vorticity in the right heart of patients after repair of tetralogy of Fallot (rTOF) compared with healthy volunteers. METHODS: Time-resolved flow-sensitive 4D MRI was acquired in 24 rTOF patients and 12 volunteers. Qualitative flow evaluation was based on consensus reading of two observers. Quantitative analysis included segmentation of the right atrium (RA) and ventricle (RV) in a four-chamber view to extract volumes and regional haemodynamic information for computation of regional mean and peak vorticity. RESULTS: Right heart intra-atrial, intraventricular and outflow tract flow patterns differed considerably between rTOF patients and volunteers. Peak RA and mean RV vorticity was significantly higher in patients (p = 0.02/0.05). Significant negative correlations were found between patients' maximum and mean RV and RA vorticity and ventricular volumes (p < 0.05). The main pulmonary artery (MPA) regurgitant flow was associated with higher RA and RV vorticity, which was significant for RA maximum and RV mean vorticity (p = 0.01/0.03). CONCLUSION: The calculation of vorticity based on 4D flow data is an alternative approach to assess intracardiac flow changes in rTOF patients compared with qualitative flow visualization. Alterations in intracardiac vorticity could be relevant with regard to the development of RV dilation and impaired function. KEY POINTS: • 4D flow MRI with vorticity calculation enables a novel approach to assess intracardiac flow. • Significantly higher intracardiac vorticity occurred in patients after repair of tetralogy of Fallot. • Regurgitant flow in the main pulmonary artery is associated with higher right heart vorticity.

Postoperative pulmonary and aortic 3D haemodynamics in patients after repair of transposition of the great arteries.

OBJECTIVES: To characterise aortic and pulmonary haemodynamics and investigate the correlation with post-surgical anatomy in patients with dextro-transposition of the great arteries (d-TGA). METHODS: Four-dimensional (4D) MRI was performed in 17 patients after switch repair of TGA and 12 healthy controls (age, 11.9 ± 5.4 vs 23.3 ± 1.6 years). Patients were divided according to the pulmonary trunk (TP) position in relation to the ascending aorta (AAo): anterior (n = 10) and right/left anterior position (n = 7). Analysis included visual grading (ranking 0-2) of pulmonary and aortic vortical and helical flow, flow velocity quantification, blood-flow distribution to the right and left pulmonary arteries (flow ratio rPA:lPA), and vessel lumen areas. RESULTS: Anterior TP position was associated with increased vortices in six out of ten patients compared with right anterior TP position (one out of seven) and controls (none). Reduced systolic lPA and TP lumina in patients resulted in significantly increased peak systolic velocities (P < 0.001). Flow ratio rPA:lPA was more heterogeneous in patients (rPA:lPA = 1.56 ± 0.78 vs volunteers 1.09 ± 0.15; P < 0.05) with predominant flow to the rPA. Eleven patients presented increased helices in the AAo (grade 1.6). CONCLUSIONS: Evaluation of post-surgical haemodynamics in TGA patients revealed increased vortical flow for anterior TP position, asymmetric flow and increased systolic flow velocity in the pulmonary arteries owing to reduced vascular lumina. KEY POINTS: • 3D phase contrast MRI with velocity encoding (4D MRI) has numerous cardiovascular applications • 4D MRI demonstrates postoperative haemodynamics following surgery for transposition of the great arteries • Flow visualisation depicted enhanced pulmonary vortices in the anterior pulmonary trunk • Narrow pulmonary arterial systolic lumina resulted in increased peak systolic velocities.

Aortic wall shear stress in Marfan syndrome.

The aim of this study was to quantify changes in thoracic aortic wall shear stress (WSS) in asymptomatic patients with Marfan syndrome (MFS) compared with healthy controls. WSS in the thoracic aorta was quantified based on time-resolved 3D phase contrast MRI with three-directional velocity encoding (4D flow MRI, temporal resolution ∼44 ms, spatial resolution ∼2.5 mm) in 24 patients with confirmed MFS (age = 18 ± 12 years) and in 12 older healthy volunteers (age = 25 ± 3 years). Diameters of the thoracic aorta normalized to body surface area were similar for both groups. Peak systolic velocity, absolute WSS, time-averaged WSS, circumferential WSS, peak systolic WSS, and WSS eccentricity were calculated in eight analysis planes distributed along the thoracic aorta. Plane-wise comparison revealed significant differences between MFS patients and volunteers in the proximal ascending aorta for peak systolic velocities (1.11 ± 0.23 m/s vs. 1.34 ± 0.18 m/s, P = 0.004) and circumferential WSS (0.14 ± 0.03 N/m(2) vs. 0.11 ± 0.02 N/m(2), P = 0.007). WSS eccentricity was altered in most of the ascending aorta and proximal arch (P = 0.009-0.020). MFS patients demonstrated segmental differences in peak systolic WSS with a significantly higher WSS at the inner curvature in the proximal ascending aorta and at the anterior part in the more distal ascending aorta (P < 0.01). These findings indicate differences in WSS associated with MFS despite similar aortic dimensions compared to controls.

4-D MRI flow analysis in the course of interrupted aortic arch reveals complex morphology and quantifies amount of collateral blood flow.

We present findings in a 17-year-old with interrupted aortic arch, in whom standard imaging techniques missed functional and morphological problems. Flow-sensitive four-dimensional magnetic resonance (4-D MR) enabled assessment of the complex anatomy and blood-flow characteristics in the entire aorta and direct quantification of blood flow in collateral vessels. Our findings highlight the entire morphological and functional problem of interrupted aortic arch and illustrate the potential of flow-sensitive 4-D MR for surgical planning in congenital heart disease.

Noninvasive evaluation of 3D hemodynamics in a complex case of single ventricle physiology.

We report the comprehensive evaluation of the complex hemodynamics in a rare case of a pediatric patient after repair of congenital heart disease with multiple abnormalities including hypoplastic left heart, double outlet right ventricle, transposition of great arteries, ventricular septal defect, aortic coarctation, and total cavopulmonary connection. Based on a single measurement, whole-heart flow-sensitive 4D magnetic resonance imaging (MRI) was able to demonstrate a number of regional flow alterations such as poststenotic helix formation and asymmetric flow distributions for the double arterial outlet and to the left and right lungs. Our findings illustrate the potential role of flow-sensitive 4D MRI as a noninvasive and radiation-free technique for the frequent postinterventional follow-up in these pediatric patients.

Aortic flow patterns in patients with Marfan syndrome assessed by flow-sensitive four-dimensional MRI.

PURPOSE: To apply time-resolved three-dimensional (3D) phase contrast MRI with three-directional velocity encoding (flow-sensitive 4D MRI) for the characterization of flow pattern changes in patients with Marfan syndrome (MFS) compared with normal controls. MATERIALS AND METHODS: Flow-sensitive 4D MRI of the thoracic aorta (temporal resolution ∼45 ms, spatial resolution ∼2.4 × 2.1 × 2.8 mm(3) ) was performed in 24 MFS patients and 10 volunteers. Aortic flow patterns were visualized by 3D particle traces and streamlines. Global (affecting the complete lumen) and local (parts of the vessel lumen) helix and vortex flow in the ascending aorta (AAo), aortic arch, and descending aorta (DAo) were graded in 3 categories (blinded reading, two observers): none = 0, moderate = 1, pronounced = 2. RESULTS: Flow grading revealed similar global helix and vortex flow in the AAo and arch for MFS patients and controls. Local helix flow in the AAo was significantly (P = 0.011) increased in patients and was associated with aortic sinus dilatation. The incidence of global helix and vortex flow in the DAo was increased in patients (77% and 50% of subjects) compared with controls (none and 10%). CONCLUSION: The 4D flow analysis revealed marked differences of the aortic flow patterns between Marfan patients and controls: Local helix flow in the patients' AAo may be associated with the increased incidence of aortic root dilatation. The flow alterations in the proximal DAo could explain the occurrence of Type-B dissection originating from this site.

In vivo noninvasive 4D pressure difference mapping in the human aorta: phantom comparison and application in healthy volunteers and patients.

In this work, we present a systematic phantom comparison and clinical application of noninvasive pressure difference mapping in the human aorta based on time-resolved 3D phase contrast data. Relative pressure differences were calculated based on integration and iterative refinement of pressure gradients derived from MR-based three-directional velocity vector fields (flow-sensitive 4D MRI with spatial/temporal resolution ∼ 2.1 mm(3)/40 ms) using the Navier-Stokes equation. After in vitro study using a stenosis phantom, time-resolved 3D pressure gradients were systematically evaluated in the thoracic aorta in a group of 12 healthy subjects and 6 patients after repair for aortic coarctation. Results from the phantom study showed good agreement with expected values and standard methods (Bernoulli). Data of healthy subjects showed good intersubject consistency and good agreement with the literature. In patients, pressure waveforms showed elevated peak values. Pressure gradients across the stenosis were compared with reference measurements from Doppler ultrasound. The MRI findings demonstrated a significant correlation (r = 0.96, P < 0.05) but moderate underestimation (14.7% ± 15.5%) compared with ultrasound when the maximum pressure difference for all possible paths connecting proximal and distal locations of the stenosis were used. This study demonstrates the potential of the applied approach to derive additional quantitative information such as pressure gradients from time-resolved 3D phase contrast MRI.

Three-dimensional flow characteristics in aortic coarctation and poststenotic dilatation.

The authors present findings from a scientific study in a 36-year-old male patient who was transferred for the evaluation of a restenosis in aortic coarctation that was initially treated by surgical repair. Contrast-enhanced magnetic resonance angiography and comprehensive flow-sensitive 4-dimensional magnetic resonance imaging for the evaluation of 3-dimensional blood flow in the entire thoracic aorta demonstrated distinct flow pattern changes associated with the disease, demonstrating a potential link between altered vascular hemodynamics and the development of vascular disease.

Multidirectional flow analysis by cardiovascular magnetic resonance in aneurysm development following repair of aortic coarctation.

Aneurysm formation is a life-threatening complication after operative therapy in coarctation. The identification of patients at risk for the development of such secondary pathologies is of high interest and requires a detailed understanding of the link between vascular malformation and altered hemodynamics. The routine morphometric follow-up by magnetic resonance angiography is a well-established technique. However, the intrinsic sensitivity of magnetic resonance (MR) towards motion offers the possibility to additionally investigate hemodynamic consequences of morphological changes of the aorta. We demonstrate two cases of aneurysm formation 13 and 35 years after coarctation surgery based on a Waldhausen repair with a subclavian patch and a Vosschulte repair with a Dacron patch, respectively. Comprehensive flow visualization by cardiovascular MR (CMR) was performed using a flow-sensitive, 3-dimensional, and 3-directional time-resolved gradient echo sequence at 3T. Subsequent analysis included the calculation of a phase contrast MR angiography and color-coded streamline and particle trace 3D visualization. Additional quantitative evaluation provided regional physiological information on blood flow and derived vessel wall parameters such as wall shear stress and oscillatory shear index. The results highlight the individual 3D blood-flow patterns associated with the different vascular pathologies following repair of aortic coarctation. In addition to known factors predisposing for aneurysm formation after surgical repair of coarctation these findings indicate the importance of flow sensitive CMR to follow up hemodynamic changes with respect to the development of vascular disease.

Aortic hemodynamics in patients with and without repair of aortic coarctation: in vivo analysis by 4D flow-sensitive magnetic resonance imaging.

OBJECTIVES: The purpose of this study was to characterize hemodynamic alterations and flow-derived vessel wall parameters in aortic coarctation (CoA) patients with and without operative repair by time-resolved, 3-dimensional, and 3-directional velocity sensitive, phase-contrast magnetic resonance imaging (4D PC MRI) in comparison with healthy subjects. METHODS AND MATERIAL: Twenty-four patients, 12.5 ± 6.4 years after CoA repair, 4 patients without treatment for CoA, and 19 healthy subjects were examined. The study was approved by the institutional review board and signature of written informed consent was obtained from the participants. Echocardiography was performed in patients before participation. MRI studies were conducted by applying flow-sensitive 4D phase-contrast MRI at either 1.5 T (n = 5 patients) or 3 T (all 19 healthy subjects, n = 23 patients). Blood flow visualization was used to evaluate overall aortic helicity, presence of pronounced or additional localized helix flow, and vortex development. Quantitative evaluation comprised the calculation of regional time-averaged absolute wall shear stress (WSS(mag)), peak velocities, and oscillatory shear index at 8 locations distributed along the thoracic aorta and additionally at the site of CoA. Inter- and intraobserver variabilities of calculations were determined. RESULTS: Volunteers and patients demonstrated the same amount of overall aortic helicity. In contrast, the number of additional localized helix flow or vortex formation was significantly increased in patients (25/28 patients vs. 5/19 normal controls, Fisher exact test: P < 0.001). Vortices in the orifices of the supra-aortic branches were detected in 64.3% (18/28) of patients but in only 11.8% (2/19) of controls (P < 0.001). Quantitative analyses revealed a significant increase in overall aortic WSS(mag) (0.44 ± 0.17 N/m(2) in patients vs. 0.27 ± 0.08 N/m(2) in volunteers, P < 0.005) and a decrease in overall oscillatory shear index. Repeated quantitative analysis showed moderate interobserver and low intraobserver variability. Correlation with echocardiography showed good agreement with MRI which tended to underestimate peak velocities (r = 0.76; Bland-Altman analysis, limits of agreement = -0.57-2.16 m/s, mean = 0.79 m/s). CONCLUSION: Alterations in aortic hemodynamics after CoA repair are not limited to the specific region of repair, but can be found in the entire aorta. The presented findings highlight the systemic nature of the disease and the need for a systemic diagnostic approach which can be provided by flow-sensitive 4D PC MRI. Furthermore, valuable additional insights on the hemodynamic consequences of coarctation have been shown that may help understanding secondary complications such as restenosis, aneurysm formation, and arterial hypertension.