Quantification of Retrograde Blood Flow in the Descending Aorta Using Transesophageal Echocardiography in Comparison to 4D Flow MRI.

BACKGROUND: Retrograde diastolic blood flow in the proximal descending aorta (DAo), which connects plaques ≥4 mm thickness with brain-supplying arteries, has previously been identified as a possible source of brain embolism. Currently, only 4D flow MRI is able to visualize and quantify potential retrograde embolization pathways in the DAo in-vivo. Hence, it was our aim to test if the extent of retrograde flow could be estimated by routine 2D transesophageal echocardiography (TEE). METHODS: Forty-eight acute stroke patients were prospectively included and they underwent Doppler examinations of the transition zone between the aortic arch and the DAo using a 20 mm 2D sample volume in longitudinal section at 90-140° Doppler angle during routine TEE. Velocity-time-integrals (VTI) were studied for antegrade and retrograde velocities and the ratio (VTIratio) was calculated and correlated with the length of retrograde pathlines at that site, which were visualized using 4D flow MRI at 3-Tesla. A receiver operating characteristic (ROC) curve was used to evaluate a threshold value of VTIratio in differentiating large (≥3 cm) from small (<3 cm) retrograde flow extent. RESULTS: At the TEE measurement site, the mean VTIratio was 0.53 ± 0.16 and the mean length of retrograde pathlines reaching back into the aortic arch was 3.1 ± 1.4 cm. VTIratio was an independent predictor of retrograde pathline length (r = 0.44; p = 0.002). ROC analysis identified a VTIratio threshold value of 0.6012 with a sensitivity of 0.5, a specificity of 0.92, and positive and negative predictive values of 0.84 and 0.68, respectively. Accordingly, 11 (22.91%) patients had a VTIratio cutoff value ≥0.6012 and corresponding retrograde pathline length ≥3 cm in 4D flow MRI. CONCLUSIONS: TEE allows predicting the length of retrograde pathlines. Hence, it may offer a cost-effective way to investigate independent predictors of DAo flow reversal in large-scale studies. However, TEE is only of limited value as a screening tool for high retrograde flow in a clinical setting, as only ∼23% of patients can be spared 4D flow MRI, which remains indispensable for the exact assessment of individual embolization pathways from plaques of the DAo in-vivo.

Prevalence of potential retrograde embolization pathways in the proximal descending aorta in stroke patients and controls.

BACKGROUND: Retrograde diastolic blood flow in the proximal descending aorta (DAo) connecting complex plaques (≥4 mm thick) with brain-supplying supra-aortic arteries may constitute a source of stroke. Yet, data only from high-risk populations (cryptogenic stroke patients with aortic atheroma≥3 mm) regarding the prevalence of this potential stroke mechanism are available. We aimed to quantify the frequency of this mechanism in unselected patients with cryptogenic stroke after routine diagnostics and controls without a history of stroke. METHODS: 88 patients (67 stroke patients, 21 cardiac controls) were prospectively included. 3D T1-weighted bright blood MRI of the aorta was applied for the detection of complex DAo atheroma. ECG-triggered and navigator-gated 4D flow MRI allowed measuring time-resolved 3D blood flow in vivo. Potential retrograde embolization pathways were defined as the co-occurrence of complex plaques and retrograde blood flow in the DAo reaching the outlet of (a) the left subclavian artery, (b) the left common carotid artery, or/and (c) the brachiocephalic trunk. The frequency of these pathways was analyzed by importing 2D plaque images into 3D blood flow visualization software. RESULTS: Complex DAo plaques were more frequent in stroke patients (44 in 31/67 patients (46.3%) vs. 5 in 4/21 controls (19.1%); p=0.039), especially in older patients (29/46 (63.04%) patients≥60 years of age with 41 plaques vs. 2/21 (9.14%) patients<60 years of age with 3 plaques; p<0.001). Contrary to our assumption, retrograde diastolic blood flow at the DAo occurred in every patient irrespective of the existence of plaques with a similar extent in both groups (26±14 vs. 32±18 mm; p=0.114). Therefore, only the higher prevalence of complex DAo plaques in stroke patients resulted in a three times higher frequency of potential retrograde embolization pathways compared to controls (22/67 (32.8%) vs. 2/21 (9.5%) controls; p=0.048). CONCLUSIONS: This study revealed that retrograde flow in the descending aorta is a common phenomenon not only in stroke patients. The existence of potential retrograde embolization pathways depends mainly on the occurrence of complex plaques in the area 0 to ∼30 mm behind the outlet of the left subclavian artery, which is exposed to flow reversal. In conclusion, we have shown that the frequency of potential retrograde embolization pathways was significantly higher in stroke patients suggesting that this mechanism may play a role in retrograde brain embolism.

Quantification of aortic stiffness in stroke patients using 4D flow MRI in comparison with transesophageal echocardiography.

To quantify stiffness of the descending aorta (DAo) in stroke patients using 4D flow MRI and compare results with transesophageal echocardiography (TEE). 48 acute stroke patients undergoing 4D flow MRI and TEE were included. Intima-media-thickness (IMT) was measured in the DAo and the aorta was scrutinized for atherosclerotic plaques using TEE. Stiffness of the DAo was determined by (a) 4D flow MRI at 3 T by calculating pulse wave velocity (PWV) and by (b) TEE calculating arterial strain, stiffness index, and distensibility coefficient. Mean IMT was 1.43 ± 1.75. 7 (14.6%) subjects had no sign of atherosclerosis, 10 (20.8%) had IMT-thickening or plaques < 4 mm, and 31 (66.7%) had at least one large and/or complex plaque in the aorta. Increased IMT significantly correlated (p < 0.001) with increased DAo stiffness in MRI (PWV r = 0.66) and in TEE (strain r = 0.57, stiffness index r = 0.64, distensibility coefficient r = 0.57). Patients with at least IMT-thickening had significantly higher stiffness values compared to patients without atherosclerosis. However, no difference was observed between patients with plaques < 4 mm and patients with plaques ≥ 4 mm. PWV and TEE parameters of stiffness correlated significantly [strain (r = - 0.36; p = 0.011), stiffness index (r = 0.51; p = 0.002), and distensibility coefficient (r = - 0.59; p < 0.001)]. 4D flow MRI and TEE-based parameters of aortic stiffness were associated with markers of atherosclerosis such as IMT-thickness and presence of plaques. We believe that 4D flow MRI is a promising tool for future studies of aortic atherosclerosis, due to its longer coverage of the aorta and non-invasiveness.

Accelerated analysis of three-dimensional blood flow of the thoracic aorta in stroke patients.

To test if new software accelerates analysis of in vivo acquired 4D flow MRI data. Respiration-gated and ECG-synchronized 4D flow MRI of the aorta was performed in 20 stroke patients using a routine 3-Tesla MRI system (TIMTRIO, Siemens, Germany). 3D blood flow data was processed by one experienced observer using new (A = MEVISFlow) and widely-used software (B = EnSight + Velomap-/FlowTool). Evaluation included: inter-/intra-observer variability of software A and inter-software comparison regarding (1) blood flow quantification (total-/peak flow) and (2) flow visualisation, plus (3) measurement of the time required for visualization and quantification of data (software A&B). (1) Inter-/intra-observer agreement of software A (mean difference ≤5.2 and ≤0.9 %, respectively) and inter-software agreement (mean difference ≤ 2.2 %) was high with high correlation of peak and total blood flow (r ≥ 0.74; p < 0.001 and r ≥ 0.91; p < 0.001). (2) Comparison of blood flow visualization showed substantial agreement (κ ≥ 0.68). (3) Data-analysis was three times faster when using software A [18:10 (±1:29) vs. 58:30 (±5:28) min; p < 0.0001]. Acceleration of blood flow quantification and visualisation using new software strongly facilitates future applications of 4D flow MRI and thus enables its usage in larger patient cohorts in clinical research and routine.