Thomas Wehrum

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.

Aortic Atherosclerosis Determines Increased Retrograde Blood Flow as a Potential Mechanism of Retrograde Embolic Stroke

Background: Retrograde brain embolization from complex plaques of the proximal descending aorta (DAo) has been identified as a new potential mechanism of stroke. Our purpose was to identify predictors of increased retrograde aortic blood flow indicating an elevated risk of brain embolization from the DAo. Methods: A total of 485 patients with acute ischemic stroke were prospectively included and underwent transesophageal echocardiography. Blood flow velocities in the proximal DAo were studied using 2D pulse-wave Doppler ultrasound. Velocity-time integrals (VTI) were calculated for antegrade and retrograde velocity directions. The ratio (VTIretrograde/VTIantegrade) was used to estimate retrograde flow extent. Associations between patient demographics, cardiovascular risk factors, echocardiographic parameters, and VTIratio were analyzed using multivariate linear regression. Results: Retrograde blood flow in the DAo occurred in all patients. Velocity profiles in the proximal DAo were as follows (mean ± SD): VTIantegrade = 21.1 ± 6.5, VTIretrograde = 11.0 ± 3.6, and VTIratio = 0.54 ± 0.16. Diameter (r = 0.25, p < 0.001), presence of complex plaques (r = 0.12, p = 0.007), and reduced strain of the DAo (r = -0.23, p < 0.001) had significant partial effects in a predictor model based on predefined variables, which predicted 26% (adjusted R2 = 0.26) of the variance in VTIratio. A unit increase in the DAo diameter was associated with a 2% increase in VTIratio (95% CI 1-2.8%, p < 0.001). Presence of complex plaques increased VTIratio by 7% (95% CI 2-13%, p = 0.007) and an increase in strain by 0.1 indicated a decrease in VTIratio by about 11% (95% CI 6.2-15.5%, p < 0.001). Complex atheroma was found in the proximal DAo of 79 subjects, of which 40 (50.6%) had a VTIratio above average (VTIratio ≥0.54) compared to 87 of 261 (33.3%) patients without any complex plaques (p < 0.001). Twenty-five of 79 (31.7%) patients with complex DAo plaques had a VTIratio ≥0.60, which indicates a high likelihood of retrograde pathline length of ≥3 cm and thus increased risk of retrograde cerebral embolization. Stroke etiology of those 25 patients was determined in 13 and cryptogenic in 12 cases. Conclusions: Retrograde blood flow in the DAo was found in all stroke patients. However, it increased further in patients with concomitant complex plaques, low strain, and/or large aortic diameter, that is, in those with atherosclerosis of the DAo. Accordingly, such patients may be predisposed to retrograde embolization in case of occurrence of a complex plaque in proximity to a brain-supplying artery.

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.

Acute Cerebral Venous Thrombosis: Three-Dimensional Visualization and Quantification of Hemodynamic Alterations Using 4-Dimensional Flow Magnetic Resonance Imaging

Background and Purpose— Cerebral venous thrombosis (CVT) affects venous hemodynamics and can provoke severe stroke and chronic intracranial hypertension. We sought to comprehensively analyze 3-dimensional blood flow and hemodynamic alterations during acute CVT including collateral recruitment and at follow-up. Methods— Twenty-two consecutive patients with acute CVT were prospectively included and underwent routine brain magnetic resonance imaging (MRI) and 4-dimensional flow MRI at 3 T for the in vivo assessment of cerebral blood flow. Neurological and MRI follow-up at 6 months was performed in 18 patients. Results— Three-dimensional blood flow visualization and quantification of large dural venous sinuses and deep cerebral veins was successfully performed in all patients. During acute CVT, we observed abnormal flow patterns including stagnant flow, flow acceleration in stenoses, and change of flow directions. In patients with complete recanalization, flow trajectories resembled those known from previously published 4-dimensional flow MRI data in healthy adults. There was a trend toward a relationship between occluded segments and cerebral lesions (not significant). Furthermore, patients with versus without cerebral lesions showed increased mean (0.08±0.09 versus 0.005±0.014 m/s) and peak velocities (0.18±0.21 versus 0.006±0.02 m/s) within partially thrombosed left and right transverse sinuses (P<0.05) at baseline. Conclusions— Four-dimensional flow MRI was successfully applied for the 3-dimensional visualization and quantification of venous hemodynamics in patients with CVT and provided new dynamic information regarding vessel recanalization. This technique seems promising to investigate the contribution of hemodynamic parameters and collaterals in a larger cohort to identify those at risk of stroke.

Multi-contrast and three-dimensional assessment of the aortic wall using 3 T MRI

OBJECTIVES To develop a 3D-multi-contrast MRI protocol allowing for high resolution imaging of the wall and of atheroma in the thoracic aorta. METHODS Eleven healthy volunteers and eleven acute stroke patients with aortic plaques detected by TEE underwent MRI at 3T. The MRI-protocol consisted of a T1w-bright-blood, a T2w- and a PDw-black-blood sequence (spatial resolution=1.15mm3). Image quality was assessed by two blinded investigators using a 3-point score and intra- and inter-rater agreement was tested. In patients, atherosclerotic plaques were graded according to the modified American Heart Association (AHA) classification. RESULTS Total examination time was 35:42±7:48min in volunteers and 41:07±3:15min in patients. Image quality was graded with the highest score in 80-94% of T1w, 89-96% of T2w and 79-86% of PDw datasets. Intra- and inter-rater reliability regarding image quality grading was high. Five stroke patients showed AHA type III lesions, three had AHA type VII and two had type VIII plaques. One patient had a vulnerable appearing AHA VI plaque. CONCLUSIONS 3D-multi-contrast MR-imaging of the aorta was performed with high image quality and in reasonable time. It allows evaluation of atherosclerotic plaque composition throughout the aortic arch and can be used to identify vulnerable plaques in acute stroke patients.

Uncertainty visualization for interactive assessment of stenotic regions in vascular structures

Abstract Stenosis refers to the thinning of the inner surface (lumen) of vascular structures. Detecting stenoses and correctly estimating their degree is crucial in clinical settings for proper treatment planning. Such a planning involves a visual assessment, which in case of vascular structures is frequently based on 3D visual representations of the vessels. However, since vessel segmentation is affected by various sources of errors and noise in the imaging and image processing pipeline, it is crucial to capture and visually convey the uncertainty in a 3D visual representation. Moreover, it is crucial to quantify how much this uncertainty affects the calculated stenotic degree, since different severities lead to different treatments. We propose a novel approach for visualizing the shape deviation of different probability levels in vascular data, where the probability levels are computed from a probabilistic segmentation approach. Our non-obstructive visual encoding is based on rendering a single opaque surface representing a probability level of the cumulative distribution function around the vessels’ centerline. The surface rendering is enhanced with cumulative information about other levels. To do so, we traverse the probability space by applying an iterative projection method both inwards and outward until we reach surface variability within a given margin. We capture the shape variability between the different probability levels using the lengths of the projection lines, the change in angular directions, and the distortion of a parametrization. They are visually encoded using color and texture mapping. Furthermore, we allow for an interactive selection of a region of interest that automatically calculates the stenotic degree and how much the uncertainty affects the most likely result. We analyze our approach in comparison to state-of-the-art methods with medical experts in a study using both real magnetic resonance (MR) and computed tomography (CT) angiography data of vertebral arteries with stenoses as well as on MR angiography data with synthetically added stenoses and stenotic uncertainties. We evaluate how well our approach can guide medical experts in their assessment of the uncertainty in vertebral stenoses.