Impact of training data composition on the generalizability of convolutional neural network aortic cross-section segmentation in four-dimensional magnetic resonance flow imaging.

BACKGROUND: Four-dimensional cardiovascular magnetic resonance flow imaging (4D flow CMR) plays an important role in assessing cardiovascular diseases. However, the manual or semi-automatic segmentation of aortic vessel boundaries in 4D flow data introduces variability and limits the reproducibility of aortic hemodynamics visualization and quantitative flow-related parameter computation. This paper explores the potential of deep learning to improve 4D flow CMR segmentation by developing models for automatic segmentation and analyzes the impact of the training data on the generalization of the model across different sites, scanner vendors, sequences, and pathologies. METHODS: The study population consists of 260 4D flow CMR datasets, including subjects without known aortic pathology, healthy volunteers, and patients with bicuspid aortic valve (BAV) examined at different hospitals. The dataset was split to train segmentation models on subsets with different representations of characteristics, such as pathology, gender, age, scanner model, vendor, and field strength. An enhanced three-dimensional U-net convolutional neural network (CNN) architecture with residual units was trained for time-resolved two-dimensional aortic cross-sectional segmentation. Model performance was evaluated using Dice score, Hausdorff distance, and average symmetric surface distance on test data, datasets with characteristics not represented in the training set (model-specific), and an overall evaluation set. Standard diagnostic flow parameters were computed and compared with manual segmentation results using Bland-Altman analysis and interclass correlation. RESULTS: The representation of technical factors, such as scanner vendor and field strength, in the training dataset had the strongest influence on the overall segmentation performance. Age had a greater impact than gender. Models solely trained on BAV patients' datasets performed well on datasets of healthy subjects but not vice versa. CONCLUSION: This study highlights the importance of considering a heterogeneous dataset for the training of widely applicable automatic CNN segmentations in 4D flow CMR, with a particular focus on the inclusion of different pathologies and technical aspects of data acquisition.

Clinical value of neuroimaging indicators of intracranial hypertension in patients with cerebral venous thrombosis.

PURPOSE: Intracranial hypertension (IH) frequently complicates cerebral venous thrombosis (CVT). Distinct neuroimaging findings are associated with IH, yet their discriminative power, reversibility and factors favoring normalization in prospective CVT patients are unknown. We determined test performance measures of neuroimaging signs in acute CVT patients, their longitudinal change under anticoagulation, association with IH at baseline and with recanalization at follow-up. METHODS: We included 26 consecutive acute CVT patients and 26 healthy controls. Patients were classified as having IH based on CSF pressure > 25 cmH2O and/or papilledema on ophthalmological examination or ocular MRI. We assessed optic nerve sheath diameter (ONSD), optic nerve tortuousity, bulbar flattening, lateral and IVth ventricle size, pituitary configuration at baseline and follow-up, and their association with IH and venous recanalization. RESULTS: 46% of CVT patients had IH. ONSD enlargement > 5.8 mm, optic nerve tortuousity and pituitary grade ≥ III had highest sensitivity, ocular bulb flattening and pituitary grade ≥ III highest specificity for IH. Only ONSD reliably discriminated IH at baseline. Recanalization was significantly associated with regressive ONSD and pituitary grade. Other neuroimaging signs tended to regress with recanalization. After treatment, 184.9 ± 44.7 days after diagnosis, bulbar flattening resolved, whereas compared with controls ONSD enlargement (p < 0.001) and partially empty sella (p = 0.017), among other indicators, persisted. CONCLUSION: ONSD and pituitary grading have a high diagnostic value in diagnosing and monitoring CVT-associated IH. Given their limited sensitivity during early CVT and potentially persistent alterations following IH, neuroimaging indicators can neither replace CSF pressure measurement in diagnosing IH, nor determine the duration of anticoagulation.

Prevalence and Therapeutic Implications of Clonal Hematopoiesis of Indeterminate Potential in Young Patients With Stroke.

BACKGROUND: Undetermined stroke etiology hampers optimal secondary prevention in a large proportion of young patients. We explored whether genetic screening for clonal hematopoiesis of indetermined potential (CHIP), a novel risk factor for stroke, could identify patients with myeloid precursor lesions or covert myeloid neoplasm requiring specific treatment. METHODS: We performed targeted sequencing on 56 genes recurrently mutated in hematologic neoplasms in a prospective cohort of patients with acute brain ischemia between 18 and 60 years. CHIP prevalence was compared with age-matched healthy controls from the Nijmegen Biomedical Study (n=1604) and the UK Biobank (n=101 678). Patients with suspicion of high-risk CHIP or myeloid neoplasm were invited for further hematologic evaluation. RESULTS: We included 248 consecutive patients (39% women) of whom 176 (71%) had cryptogenic stroke etiology. Fifty-one (21%) patients had CHIP, 3-fold more than in the general population (7.7% versus 2.6% for the Nijmegen Biomedical Study and 11.9% versus 4.1% for UK Biobank; P<0.001 for both). Patients with CHIP were older (median [interquartile range], 53 [50-59] versus 51 [41-56] years; P<0.001), had higher carotid intima-media thickness (0.68 [0.58-0.80] versus 0.59 [0.51-0.73] mm; P=0.009), and had higher burden of atherosclerosis (29.4% versus 16.7%; P=0.04). We invited 11 patients (4.4%) for further hematologic assessment, which in 7 led to the diagnosis of high-risk CHIP and in 2 to the new diagnosis of a myeloproliferative neoplasm with indication for cytoreductive therapy. CONCLUSIONS: Using genetic screening for myeloid disorders in patients with stroke of predominantly undetermined etiology, we found a 3-fold higher CHIP prevalence than in the general population. We identified high-risk CHIP and previously covert myeloproliferative neoplasms as potential stroke etiologies in 4.4% and 1% of patients, respectively. Our findings demonstrate the diagnostic and therapeutic yield of genetic screening in young patients with stroke. Future studies should investigate the role of CHIP for stroke recurrence and optimal secondary prevention.

Genetically predicted on-statin LDL response is associated with higher intracerebral haemorrhage risk.

Statins lower low-density lipoprotein cholesterol and are widely used for the prevention of atherosclerotic cardiovascular disease. Whether statin-induced low-density lipoprotein reduction increases risk of intracerebral haemorrhage has been debated for almost two decades. Here, we explored whether genetically predicted on-statin low-density lipoprotein response is associated with intracerebral haemorrhage risk using Mendelian randomization. Using genomic data from randomized trials, we derived a polygenic score from 35 single nucleotide polymorphisms of on-statin low-density lipoprotein response and tested it in the population-based UK Biobank. We extracted statin drug and dose information from primary care data on a subset of 225 195 UK Biobank participants covering a period of 29 years. We validated the effects of the genetic score on longitudinal low-density lipoprotein measurements with generalized mixed models and explored associations with incident intracerebral haemorrhage using Cox regression analysis. Statins were prescribed at least once to 75 973 (31%) of the study participants (mean 57 years, 55% females). Among statin users, mean low-density lipoprotein decreased by 3.45 mg/dl per year [95% confidence interval (CI): (-3.47, -3.42)] over follow-up. A higher genetic score of statin response [1 standard deviation (SD) increment] was associated with significant additional reductions in low-density lipoprotein levels [-0.05 mg/dl per year, (-0.07, -0.02)], showed concordant lipidomic effects on other lipid traits as statin use and was associated with a lower risk for incident myocardial infarction [hazard ratio per SD increment 0.98 95% CI (0.96, 0.99)] and peripheral artery disease [hazard ratio per SD increment 0.93 95% CI (0.87, 0.99)]. Over a 11-year follow-up period, a higher genetically predicted statin response among statin users was associated with higher intracerebral haemorrhage risk in a model adjusting for statin dose [hazard ratio per SD increment 1.16, 95% CI (1.05, 1.28)]. On the contrary, there was no association with intracerebral haemorrhage risk among statin non-users (P = 0.89). These results provide further support for the hypothesis that statin-induced low-density lipoprotein reduction may be causally associated with intracerebral haemorrhage risk. While the net benefit of statins for preventing vascular disease is well-established, these results provide insights about the personalized response to statin intake and the role of pharmacological low-density lipoprotein lowering in the pathogenesis of intracerebral haemorrhage.

Acute Stroke in Times of the COVID-19 Pandemic: A Multicenter Study.

BACKGROUND AND PURPOSE: This study aims to assess the number of patients with acute ischemic cerebrovascular events seeking in-patient medical emergency care since the implementation of social distancing measures in the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this retrospective multicenter study, data on the number of hospital admissions due to acute ischemic stroke or transient ischemic attack and numbers of reperfusion therapies performed in weeks 1 to 15 of 2020 and 2019 were collected in 4 German academic stroke centers. Poisson regression was used to test for a change in admission rates before and after the implementation of extensive social distancing measures in week 12 of 2020. The analysis of anonymized regional mobility data allowed for correlations between changes in public mobility as measured by the number and length of trips taken and hospital admission for stroke/transient ischemic attack. RESULTS: Only little variation of admission rates was observed before and after week 11 in 2019 and between the weeks 1 and 11 of 2019 and 2020. However, reflecting the impact of the COVID-19 pandemic, a significant decrease in the number of admissions for transient ischemic attack was observed (-85%, -46%, -42%) in 3 of 4 centers, while in 2 of 4 centers, stroke admission rates decreased significantly by 40% and 46% after week 12 in 2020. A relevant effect on reperfusion therapies was found for 1 center only (thrombolysis, -60%; thrombectomy, -61%). Positive correlations between number of ischemic events and mobility measures in the corresponding cities were identified for 3 of 4 centers. CONCLUSIONS: These data demonstrate and quantify decreasing hospital admissions due to ischemic cerebrovascular events and suggest that this may be a consequence of social distancing measures, in particular because hospital resources for acute stroke care were not limited during this period. Hence, raising public awareness is necessary to avoid serious healthcare and economic consequences of undiagnosed and untreated strokes and transient ischemic attacks.

Hemodynamics of cerebral veins analyzed by 2d and 4d flow mri and ultrasound in healthy volunteers and patients with multiple sclerosis.

BACKGROUND: Hemodynamic alterations of extracranial veins are considered an etiologic factor in multiple sclerosis (MS). However, ultrasound and MRI studies could not confirm a pathophysiological link. Because of technical challenges using standard diagnostics, information about the involvement of superficial intracranial veins in proximity to the affected brain in MS is scarce. PURPOSE: To comprehensively investigate the hemodynamics of intracranial veins and of the venous outflow tract in MS patients and controls. STUDY TYPE: Prospective. POPULATION: Twenty-eight patients with relapsing-remitting MS (EDSS1.9 ± 1.1; range 0-3) and 41 healthy controls. FIELD STRENGTH/SEQUENCE: 3T/2D phase-contrast and time-resolved 4D flow MRI, extra- and transcranial sonography. ASSESSMENT: Hemodynamics within the superficial and deep intracranial venous system and outflow tract including the internal, basal, and great cerebral vein, straight, superior sagittal, and transverse sinuses, internal jugular and vertebral veins. Sonography adhered to the chronic cerebrospinal venous insufficiency (CCSVI) criteria. STATISTICAL TESTS: Multivariate repeated measure analysis of variance, Student's two-sample t-test, chi-square, Fisher's exact test; separate analysis of the entire cohort and 32 age- and sex-matched participants. RESULTS: Multi- and univariate main effects of the factor group (MS patient vs. control) and its interactions with the factor vessel position (lower flow within dorsal superior sagittal sinus in MS, 3 ± 1 ml/s vs. 3.8 ± 1 ml/s; P < 0.05) in the uncontrolled cohort were attributable to age-related differences. Age- and sex-matched pairs showed a different velocity gradient in a single segment within the deep cerebral veins (great cerebral vein, vena cerebri magna [VCM] 7.6 ± 1.7 cm/s; straight sinus [StS] 10.5 ± 2.2 cm/s vs. volunteers: VCM 9.2 ± 2.3 cm/s; StS 10.2 ± 2.3 cm/s; P = 0.01), reaching comparable velocities instantaneously downstream. Sonography was not statistically different between groups. DATA CONCLUSION: Consistent with previous studies focusing on extracranial hemodynamics, our comprehensive analysis of intracerebral venous blood flow did not reveal relevant differences between MS patients and controls. Level of Evidence 1. Technical Efficacy Stage 3. J. Magn. Reson. Imaging 2020;51:205-217.

Carotid geometry is an independent predictor of wall thickness - a 3D cardiovascular magnetic resonance study in patients with high cardiovascular risk.

BACKGROUND: The posterior wall of the proximal internal carotid artery (ICA) is the predilection site for the development of stenosis. To optimally prevent stroke, identification of new risk factors for plaque progression is of high interest. Therefore, we studied the impact of carotid geometry and wall shear stress on cardiovascular magnetic resonance (CMR)-depicted wall thickness in the ICA of patients with high cardiovascular disease risk. METHODS: One hundred twenty-one consecutive patients ≥50 years with hypertension, ≥1 additional cardiovascular risk factor and ICA plaque ≥1.5 mm thickness and < 50% stenosis were prospectively included. High-resolution 3D-multi-contrast (time of flight, T1, T2, proton density) and 4D flow CMR were performed for the assessment of morphological (bifurcation angle, ICA/common carotid artery (CCA) diameter ratio, tortuosity, and wall thickness) and hemodynamic parameters (absolute/systolic wall shear stress (WSS), oscillatory shear index (OSI)) in 242 carotid bifurcations. RESULTS: We found lower absolute/systolic WSS, higher OSI and increased wall thickness in the posterior compared to the anterior wall of the ICA bulb (p < 0.001), whereas this correlation disappeared in ≥10% stenosis. Higher carotid tortuosity (regression coefficient = 0.764; p < 0.001) and lower ICA/CCA diameter ratio (regression coefficient = - 0.302; p < 0.001) were independent predictors of increased wall thickness even after adjustment for cardiovascular risk factors. This association was not found for bifurcation angle, WSS or OSI in multivariate regression analysis. CONCLUSIONS: High carotid tortuosity and low ICA diameter were independent predictors for wall thickness of the ICA bulb in this cross-sectional study, whereas this association was not present for WSS or OSI. Thus, consideration of geometric parameters of the carotid bifurcation could be helpful to identify patients at increased risk of carotid plaque generation. However, this association and the potential benefit of WSS measurement need to be further explored in a longitudinal study.

Retrograde aortic blood flow as a mechanism of stroke: MR evaluation of the prevalence in a population-based study.

OBJECTIVES: Retrograde blood flow from complex atheroma in the descending aorta (DAo) has only recently been described as a potential mechanism of stroke. However, prevalence of this mechanism in the general population and the exact factors influencing stroke risk are unclear. METHODS: One hundred twenty-six consecutively recruited inhabitants of Freiburg, Germany, between 20 and 80 years of age prospectively underwent 3-T MRI. Aortic plaque location and thickness were determined by 3D T1 MRI (1 mm3). 4D flow MRI (spatial/temporal resolution 2 mm3/20 ms) and dedicated software were used to determine prevalence and extent of flow reversal and potential embolization from DAo plaques. Flow was correlated with baseline characteristics and echocardiographic and MRI parameters (aortic diameter, wall thickness, and pulse wave velocity). RESULTS: The maximum length of retrograde blood flow connecting the DAo with the left subclavian artery (LSA) increased from 16.1 ± 8.3 mm in 20-29-year-old to 24.7 ± 11.7 mm in 70-80-year-old subjects, correlated with age (r = 0.37; p < 0.001), and was lower in females (p = 0.003). Age was the only independent predictor of increased flow reversal. Complex DAo plaques ≥ 4-mm thickness were found in eight subjects (6.3%) and were connected with the LSA, left common carotid artery, and brachiocephalic trunk in 8 (100%), 1 (12.5%), and 0 (0%) cases, respectively. CONCLUSIONS: Retrograde blood flow from the DAo was very frequent. However, potential retrograde embolization was rare due to the low incidence of complex DAo plaques. The magnitude of flow reversal and prevalence of complex atheroma increased with age. Thus, older patients with aortic atherosclerosis are especially vulnerable to this stroke mechanism. KEY POINTS: • 4D flow MRI allows in vivo visualization and quantification of individual and three-dimensional blood flow patterns within the thoracic aorta including retrograde components. • This population-based study showed that blood flow reversal from the proximal descending aorta to the brain-supplying great arteries is very frequent and able to reach all brain territories. The extent of such flow reversal increases with age and with the extent of aortic atherosclerosis. • The combination of blood flow reversal with plaque rupture in the proximal descending aorta constitutes a potential stroke mechanism that should be considered in future trials and in the management of stroke patients in clinical routine.

Outcome of Near-Infrared Spectroscopy-Guided Selective Shunting During Carotid Endarterectomy in General Anesthesia.

BACKGROUND: To analyze the outcome of near-infrared spectroscopy (NIRS)-guided selective shunting during carotid endarterectomy and the procedural outcome. METHODS: In this retrospective single-center study, patients undergoing carotid endarterectomy in general anesthesia and receiving bihemispheric NIRS as single neuromonitoring tool between January 2009 and January 2014 were included. Shunting was applied if the reduction in the NIRS values after cross-clamping on the ipsilateral side exceeded 15%. Patients with contralateral occlusion of the internal carotid artery (ICA) were excluded, as were patients operated on by surgeons performing routine shunting. All patients underwent intraoperative angiography after vessel recanalization. RESULTS: NIRS trend was available in 441 patients. Twenty-eight were excluded from this study (14 due to preference for general shunting, 13 due to contralateral ICA occlusion, and 1 due to intraoperative ICA occlusion), resulting in a final sample of 413 patients. We observed a >15% drop in NIRS values on the ipsilateral side in 29 (7%) patients. Accordingly, an intraluminal shunt was placed into the ICA. Shunting was not performed in 384 patients (<15% drop in NIRS values). Interestingly, the NIRS values on the contralateral side were significantly elevated after cross-clamping compared with baseline in the group without shunt (P < 0.0001). On the contrary, patients requiring an ICA shunt revealed a statistically significant reduction in the rSO2 on the contralateral side compared with the baseline (after ipsilateral clamping) (P = 0.047). Three patients overall suffered a stroke, all of whom were in the no-shunt group (combined stroke rate of 0.8% [3/384] with no significant intergroup difference). There was no difference in morbidity factors between the two groups. However, surgical revision after intraoperative angiography was significantly more frequent in the shunt group (17.2%, 5/29) versus the no-shunt group (6%, 23/384), (P < 0.037). CONCLUSIONS: An NIRS-guided selective shunting strategy was associated with excellent clinical outcomes and has the potential to identify patients at risk for hypoperfusion during the clamping period. However, a potentially shunt-associated higher rate of requiring local revisions (due to flaps, twisting, stenosis, and kinking) in ICA was observed. Additional studies are needed to further refine cut-off values for NIRS, indicating the need for shunting.

Determination of aortic stiffness using 4D flow cardiovascular magnetic resonance - a population-based study.

BACKGROUND: Increased aortic stiffness is an independent predictor of cardiovascular disease. Optimal measurement is highly beneficial for the detection of atherosclerosis and the management of patients at risk. Thus, it was our purpose to selectively measure aortic stiffness using a novel imaging method and to provide reference values from a population-based study. METHODS: One hundred twenty six inhabitants of Freiburg, Germany, between 20 and 80 years prospectively underwent 3 Tesla cardiovascular magnetic resonance (CMR) of the thoracic aorta. 4D flow CMR (spatial/temporal resolution 2mm3/20ms) was executed to calculate aortic pulse wave velocity (PWV) in m/s using dedicated software. In addition, we calculated distensibility coefficients (DC) using 2D CINE CMR imaging of the ascending (AAo) and descending aorta (DAo). Segmental aortic diameter and thickness of aortic plaques were determined by 3D T1 weighted CMR (spatial resolution 1mm3). RESULTS: PWV increased from 4.93 ± 0.54 m/s in 20-30 year-old to 8.06 ± 1.03 m/s in 70-80 year-old subjects. PWV was significantly lower in women compared to men (p < 0.0001). Increased blood pressure (systolic r = 0.36, p < 0.0001; diastolic r = 0.33, p = 0.0001; mean arterial pressure r = 0.37, p < 0.0001) correlated with PWV after adjustment for age and gender. Finally, PWV increased with increasing diameter of the aorta (ascending aorta r = 0.20, p = 0.026; aortic arch r = 0.24, p = 0.009; descending aorta r = 0.26, p = 0.004). Correlation of PWV and DC of the AAo and DAo or the mean of both was high (r = 0.69, r = 0.68, r = 0.73; p < 0.001). CONCLUSIONS: 4D flow CMR was successfully applied to calculate aortic PWV and thus aortic stiffness. Findings showed a high correlation with distensibility coefficients representing local compliance of the aorta. Our novel method and reference data for PWV may provide a reliable biomarker for the identification of patients with underlying cardiovascular disease and optimal guidance of future treatment in studies or clinical routine.

Age-related changes of right atrial morphology and inflow pattern assessed using 4D flow cardiovascular magnetic resonance: results of a population-based study.

BACKGROUND: To assess age-related changes of blood flow and geometry of the caval veins and right atrium (RA) using 4D flow cardiovascular magnetic resonance (CMR) data obtained in a population-based study. METHODS: An age-stratified sample (n = 126) of the population of the city of Freiburg, Germany, underwent transthoracic echocardiography and electrocardiogram-triggered and navigator-gated 4D flow CMR at 3 Tesla covering the caval veins and right heart. Study participants were divided into three age groups (1:20-39; 2:40-59; and 3:60-80 years of age). Analysis planes were placed in the superior and inferior caval vein. Subsequently, RA morphology and three-dimensional blood inflow pattern was assessed. RESULTS: Blood flow of the RA showed a clockwise rotating helix without signs of turbulence in younger subjects. By contrast, such rotation was absent in 12 subjects of group 3 and turbulences were significantly more frequent (p < 0.001). We observed an age-related shift of the caval vein axis. While the outlets of the superior and inferior caval veins were facing each other in group 1, lateralization occurred in older subjects (p < 0.001). A convergence of axes was observed from lateral view with facing axes in older subjects (p = 0.004). Finally, mean and peak systolic blood flow in the caval veins decreased with age (group 3 < 2 < 1). CONCLUSIONS: We have provided reference values of 4D CMR blood flow for different age groups and demonstrated the significant impact of age on hemodynamics of the RA inflow tract. This effect of aging should be taken into account when assessing pathologic conditions of the heart in the future.

Reversal of dabigatran using idarucizumab: single center experience in four acute stroke patients.

Dabigatran is a direct thrombin inhibitor and a non-vitamin-K-antagonizing oral anticoagulant, approved for the prevention of stroke and systemic embolization in atrial fibrillation. Idarucizumab is a humanized monoclonal antibody that was recently approved for antagonizing the anticoagulant effects of dabigatran. Here, we report the use of idarucizumab in four acute stroke patients treated with dabigatran in order to enable intravenous thrombolysis in three patients and emergent trepanation in one patient with space occupying subdural hematoma. Since experience on the optimal management of acute stroke patients under medication with dabigatran and on the use of idarucizumab is currently limited, we propose an approach for laboratory testing and fast administration of intravenous thrombolysis and neurosurgery based on our experience.

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.

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.

Aortic atheroma as a source of stroke - assessment of embolization risk using 3D CMR in stroke patients and controls.

BACKGROUND: It was our purpose to identify vulnerable plaques in the thoracic aorta using 3D multi-contrast CMR and estimate the risk of cerebral embolization using 4D flow CMR in cryptogenic stroke patients and controls. METHODS: One hundred patients (40 with cryptogenic stroke, 60 ophthalmologic controls matched for age, sex and presence of hypertension) underwent a novel 3D multi-contrast (T1w, T2w, PDw) CMR protocol at 3 Tesla for plaque detection and characterization within the thoracic aorta, which was combined with 4D flow CMR for mapping potential embolization pathways. Plaque morphology was assessed in consensus reading by two investigators and classified according to the modified American-Heart-Association (AHA) classification of atherosclerotic plaques. RESULTS: In the thoracic aorta, plaques <4 mm thickness were found in a similar number of stroke patients and controls [23 (57.5%) versus 33 (55.0%); p = 0.81]. However, plaques ≥4 mm were more frequent in stroke patients [22 (55.0%) versus 10 (16.7%); p < 0.001]. Of those patients with plaques ≥4 mm, seven (17.5%) stroke patients and two (3.3%) controls (p < 0.001) had potentially vulnerable AHA type VI plaques. Six stroke patients with vulnerable AHA type VI plaques ≥4 mm had potential embolization pathways connecting the plaque, located in the aortic arch (n = 3) and proximal descending aorta (n = 3), with the individual territory of stroke, which made them the most likely source of stroke in those patients. CONCLUSIONS: Our findings underline the significance of ≥4 mm thick and vulnerable plaques in the aortic arch and descending aorta as a relevant etiology of stroke. CLINICAL TRIAL REGISTRATION: Unique identifier: DRKS00006234 ; date of registration: 11/06/2014.

Age dependence of pulmonary artery blood flow measured by 4D flow cardiovascular magnetic resonance: results of a population-based study.

BACKGROUND: It was our aim to systematically analyze pulmonary artery blood flow within different age-groups in the general population using 4D flow cardiovascular magnetic resonance (CMR) in order to provide a context for interpreting results of future studies (e.g., in pulmonary hypertension) using this technique. METHODS: An age-stratified sample (n = 126) of the population of the city of Freiburg, Germany, underwent ECG-triggered and navigator-gated 4D flow CMR at 3 T of the pulmonary arteries and the thoracic aorta. Analysis planes were placed in the main, left, and right pulmonary artery using dedicated software. Study participants were divided into three groups (1:20-39; 2:40-59; and 3:60-80 years of age). Subsequently, pulmonary blood flow was visualized, quantified and compared between groups. RESULTS: Time-to-peak of systolic antegrade flow was shorter, peak and average velocities and flow volumes were lower in older subjects. At the end of systole, retrograde flow in the main pulmonary artery was observed in all but one subject. Subsequently, a second antegrade flow peak occurred in diastole which was lower in older subjects. Age was an independent predictor of hemodynamic change after adjustment for cardiovascular risk factors and body-mass-index. During systole, abnormal vortices occurred in the main pulmonary artery in four male subjects. CONCLUSIONS: Comprehensive analysis of pulmonary blood flow was feasible in all subjects. We were able to detect an independent effect of ageing on pulmonary hemodynamics reflecting increased vessel stiffness and reduced pulmonary circulation. Findings of this study may be helpful for discriminating physiological from pathological flow in patients with pulmonary diseases in the future.