Publications by authors named "Andreas Harloff"

77 Publications

Dural Arteriovenous Fistula Formation Secondary to Cerebral Venous Thrombosis: Longitudinal Magnetic Resonance Imaging Assessment Using 4D-Combo-MR-Venography.

Thromb Haemost 2021 Mar 3. Epub 2021 Mar 3.

Department of Neuroradiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background And Purpose:  Dural arteriovenous fistulae (DAVFs) can develop secondary to cerebral venous thrombosis (CVT). The incidence of DAVF has not yet been investigated prospectively.

Methods:  Between July 2012 and January 2018, combined static and dynamic 4D MR venography (4D-combo-MRV) was performed in 24 consecutive patients at diagnosis of CVT and after 6 months. 3 Tesla magnetic resonance imaging with time of flight and contrast-enhanced magnetization-prepared rapid acquisition with gradient echo were performed at baseline to evaluate the extent of thrombosis and affected vessel segments. Baseline and follow-up 4D-combo-MRV were assessed for signs of DAVF. Interrater reliability of DAVF detection and the extent of recanalization were analyzed with kappa statistics.

Results:  DAVFs were detected in 4/30 CVT patients (13.3%, 95% confidence interval [CI] 3.3-26.7). Two of 24 patients (8.3%, 95% CI: 0-20.8) had coincidental DAVF with CVT on admission. At follow-up, de novo formation of DAVF following CVT was seen in 2/24 patients (8.3%, 95% CI: 0-20.8). Both de novo DAVFs were low grade and benign fistulae (Cognard type 1, 2a), which had developed at previously thrombosed segments. Endovascular treatment was required in two high degree lesions (Cognard 2a + b) detected at baseline and in one de novo DAVF (Cognard 1) because of debilitating headache and tinnitus. Thrombus load, vessel recanalization, and frequency of cerebral lesions (hemorrhage, ischemia) were not associated with DAVF occurrence.

Conclusion:  This exploratory study showed that de novo DAVF formation occurs more frequently than previously described. Although de novo DAVFs were benign, 75% of all detected DAVFs required endovascular treatment. Therefore, screening for DAVF by dynamic MRV, such as 4D-combo-MRV, seems worthwhile in CVT patients.
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http://dx.doi.org/10.1055/s-0041-1723991DOI Listing
March 2021

Influence of Pulse Wave Velocity on Atherosclerosis and Blood Flow Reversal in the Aorta: A 4-Dimensional Flow Magnetic Resonance Imaging Study in Acute Stroke Patients and Matched Controls.

J Thorac Imaging 2021 Jan 21. Epub 2021 Jan 21.

Departments of Neurology Radiology-Medical Physics, Medical Center Eye Center, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Institute for Imaging Science and Computational Modelling in Cardiovascular Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Background: Aortic stiffness is associated with a higher incidence of cardiovascular events including stroke. The primary aim of this study was to evaluate whether increased pulse wave velocity (PWV), a marker of stiffness, is an independent predictor of aortic atheroma. The secondary aim was to test whether increased PWV reinforces retrograde blood flow from the descending aorta (DAo), a mechanism of stroke.

Methods: We performed a cross-sectional case-control study with prospective data acquisition. In all, 40 stroke and 60 ophthalmic patients matched for age and cardiovascular risk factors were included. Multicontrast magnetic resonance imaging (MRI) protocol of the aorta tailored to allow a detailed plaque analysis using 3-dimensional (D) T1-weighted bright blood, T2-weighted and proton density-weighted black blood, and hemodynamic assessment using 4D flow MRI was applied. Individual PWV was calculated based on 4D flow MRI data using the time-to-foot of the blood flow waveform. The extent of maximum retrograde blood flow from the proximal DAo into the arch was quantified.

Results: PWV was higher in stroke patients compared with controls (7.62±2.59 vs. 5.96±2.49 m/s; P=0.005) and in patients with plaques (irrespective of thickness) compared with patients without plaques (7.47±2.89 vs. 5.62±1.89 m/s; P=0.002). Increased PWV was an independent predictor of plaque prevalence and contributed significantly to a predictor model explaining 36.5% (Nagelkerke R2) of the variance in plaque presence. Maximum retrograde flow extent from the proximal DAo was not correlated with PWV.

Conclusions: Aortic stiffness was higher in stroke patients and associated with a higher prevalence of plaques. Increased PWV was an independent predictor of plaque presence. Accordingly, regional PWV seems to be a valuable biomarker for the assessment and management of aortic atherosclerosis. However, no association was found for increased retrograde flow extent from the DAo.
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http://dx.doi.org/10.1097/RTI.0000000000000580DOI Listing
January 2021

Who Should Rather Undergo Transesophageal Echocardiography to Determine Stroke Etiology: Young or Elderly Stroke Patients?

Front Neurol 2020 18;11:588151. Epub 2020 Dec 18.

Department of Neurology and Neurophysiology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany.

The indication of transesophageal echocardiography (TEE) in acute stroke is unclear. Thus, we systematically studied the impact of TEE on determining stroke etiology and secondary prevention in patients of different age-groups with cryptogenic stroke. Four hundred and eighty five consecutive patients with acute retinal or cerebral ischemia were prospectively included and underwent routine stroke workup including TEE. Stroke etiology was identified according to the TOAST classification and patients were divided in those with determined and cryptogenic stroke etiology without TEE results. Then, the frequency of high- and potential-risk sources in TEE was evaluated in <55, 55-74, and ≥75 year-old patients with cryptogenic stroke etiology. Without TEE, stroke etiology was cryptogenic in 329(67.8%) patients and TEE determined possible etiology in 158(48.4%) of them. In patients aged <55, 55-74, ≥75, TEE detected aortic arch plaques ≥4 mm thickness in 2(1.2%), 37(23.0%), and 33(40.2%) and plaques with superimposed thrombi in 0(0.0%), 5(3.1%), and 7(8.5%); left atrial appendage peak emptying flow velocity ≤30cm/s in 0(0.0%), 1(0.6%), and 2(2.4%), spontaneous echo contrast in 0(0.0%), 1(0.6%), and 6(7.3%), endocarditis in 0(0.0%), 0(0.0%), and 1(1.2%) and patent foramen ovale (PFO) plus atrial septum aneurysm (ASA) in 18(20.9%), 32(19.9%), and 14(17.1%), respectively. TEE changed secondary prevention in 16.4% of these patients following guidelines of 2010/11 and still 9.4% when applying the guidelines of 2020. TEE was highly valuable for determining stroke etiology and influenced individual secondary prevention based on available treatment guidelines and expert opinion in most cases. In young patients the impact of TEE was limited to the detection of septal anomalies. By contrast, in older patients TEE detected high numbers of complex aortic atheroma and potential indicators of paroxysmal atrial fibrillation.
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http://dx.doi.org/10.3389/fneur.2020.588151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775476PMC
December 2020

Complicated Carotid Artery Plaques as a Cause of Cryptogenic Stroke.

J Am Coll Cardiol 2020 11;76(19):2212-2222

Department of Radiology, University Hospital, LMU Munich, Munich, Germany; Radiologisches Zentrum Rosenheim, Rosenheim, Germany.

Background: The underlying etiology of ischemic stroke remains unknown in up to 30% of patients.

Objectives: This study explored the causal role of complicated (American Heart Association-lesion type VI) nonstenosing carotid artery plaques (CAPs) in cryptogenic stroke (CS).

Methods: CAPIAS (Carotid Plaque Imaging in Acute Stroke) is an observational multicenter study that prospectively recruited patients aged older than 49 years with acute ischemic stroke that was restricted to the territory of a single carotid artery on brain magnetic resonance imaging (MRI) and unilateral or bilateral CAP (≥2 mm, NASCET [North American Symptomatic Carotid Endarterectomy Trial] <70%). CAP characteristics were determined qualitatively and quantitatively by high-resolution, contrast-enhanced carotid MRI at 3T using dedicated surface coils. The pre-specified study hypotheses were that that the prevalence of complicated CAP would be higher ipsilateral to the infarct than contralateral to the infarct in CS and higher in CS compared with patients with cardioembolic or small vessel stroke (CES/SVS) as a combined reference group. Patients with large artery stroke (LAS) and NASCET 50% to 69% stenosis served as an additional comparison group.

Results: Among 234 recruited patients, 196 had either CS (n = 104), CES/SVS (n = 79), or LAS (n = 19) and complete carotid MRI data. The prevalence of complicated CAP in patients with CS was significantly higher ipsilateral (31%) to the infarct compared with contralateral to the infarct (12%; p = 0.0005). Moreover, the prevalence of ipsilateral complicated CAP was significantly higher in CS (31%) compared with CES/SVS (15%; p = 0.02) and lower in CS compared with LAS (68%; p = 0.003). Lipid-rich and/or necrotic cores in ipsilateral CAP were significantly larger in CS compared with CES/SVS (p < 0.05).

Conclusions: These findings substantiate the role of complicated nonstenosing CAP as an under-recognized cause of stroke. (Carotid Plaque Imaging in Acute Stroke [CAPIAS]; NCT01284933).
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http://dx.doi.org/10.1016/j.jacc.2020.09.532DOI Listing
November 2020

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

J Cardiovasc Magn Reson 2020 09 10;22(1):67. Epub 2020 Sep 10.

Department of Neurology and Neurophysiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacherstrasse 64, 79106, Freiburg, Germany.

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.
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http://dx.doi.org/10.1186/s12968-020-00657-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488078PMC
September 2020

Optic Nerve Head Volumetry by Optical Coherence Tomography in Papilledema Related to Idiopathic Intracranial Hypertension.

Transl Vis Sci Technol 2020 02 21;9(3):24. Epub 2020 Feb 21.

Department of Neuroophthalmology, Eye Center, Medical Center, Medical Faculty, University of Freiburg, Germany.

Purpose: Idiopathic intracranial hypertension (IIH) leads to optic nerve head swelling and optic atrophy if left untreated. We wanted to assess an easy to perform volumetric algorithm to detect and quantify papilledema in comparison to retinal nerve fiber layer (RNFL) analysis using optical coherence tomography (OCT).

Methods: Participants with and without IIH underwent visual acuity testing at different contrast levels and static perimetry. Spectralis-OCT measurements comprised standard imaging of the peripapillary RNFL and macular ganglion cell layer (GCL). The optic nerve head volume (ONHV) was determined using the standard segmentation software and the 3.45 mm early treatment diabetic retinopathy study (ETDRS) grid, necessitating manual correction within Bruch membrane opening. Three neuro-ophthalmologists graded fundus images according to the Frisén scale. A mixed linear model (MLM) was used to determine differences between study groups. Sensitivity and specificity was evaluated using the area under the receiver-operating characteristic (ROC).

Results: Twenty-one patients with IIH had an increased ONHV of 6.46 ± 2.36 mm as compared to 25 controls with 3.20 ± 0.25 mm ( < 0.001). The ONHV cutoff distinguishing IIH from controls was 3.97 mm (i.e. no patient with IIH had an ONHV below and no healthy individual above this value). The area under the curve (AUC) for ONHV was 0.99 and for the RNFL at 3.5 mm 0.90. The Frisén scale grading correlated higher with the ONHV (r = 0.90) than with the RNFL thickness (r = 0.68). ONHV measurements were highly reproducible in both groups (coefficient of variation <0.01%).

Conclusions: OCT-based volumetry of the optic nerve head discriminates very accurately between individuals with and without IIH. It may serve as a useful adjunct to the rating with the subjective and ordinal Frisén scale.

Translational Relevance: A simple OCT protocol run on the proprietary software of a commercial OCT device can reliably discriminate between normal optic nerve heads or pseudo-papilledema and true papilledema while being highly reproducible. Our normative data and OCT preset may be used in further clinical studies.
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http://dx.doi.org/10.1167/tvst.9.3.24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354856PMC
February 2020

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

Stroke 2020 07 9;51(7):2224-2227. Epub 2020 Jun 9.

Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Germany (C. Hoyer, A.E., M.P., K.S.).

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.
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http://dx.doi.org/10.1161/STROKEAHA.120.030395DOI Listing
July 2020

Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany-Updated series of 120 cases.

Int J Stroke 2020 Aug 19;15(6):609-618. Epub 2020 Jan 19.

Department for Neurology, Klinikum rechts der Isar, TU München, München, Germany.

Background: Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran reversing its anticoagulant effects within minutes. Thereby, patients with acute ischemic stroke who are on dabigatran treatment may become eligible for thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). In patients on dabigatran with intracerebral hemorrhage idarucizumab could prevent lesion growth.

Aims: To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of acute ischemic stroke or intracranial hemorrhage.

Methods: Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January 2016 to August 2018 were used.

Results: One-hundred and twenty stroke patients received idarucizumab in 61 stroke centers. Eighty patients treated with dabigatran presented with ischemic stroke and 40 patients suffered intracranial bleeding (intracerebral hemorrhage (ICH) in  = 27). In patients receiving intravenous thrombolysis with rt-PA following idarucizumab, 78% showed a median improvement of 7 points in National Institutes of Health Stroke Scale. No bleeding complications were reported. Hematoma growth was observed in 3 out of 27 patients with ICH. Outcome was favorable with a median National Institutes of Health Stroke Scale improvement of 4 points and modified Rankin score 0-3 in 61%. Six out of 40 individuals (15%) with intracranial bleeding died during hospital stay.

Conclusion: Administration of rt-PA after reversal of dabigatran activity with idarucizumab in case of acute ischemic stroke seems feasible, effective, and safe. In dabigatran-associated intracranial hemorrhage, idarucizumab appears to prevent hematoma growth and to improve outcome.
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http://dx.doi.org/10.1177/1747493019895654DOI Listing
August 2020

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

Ann Vasc Surg 2019 Nov 10;61:170-177. Epub 2019 Jul 10.

Department of Cardiovascular Surgery, Heart Centre Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany.

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 rSO 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.
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http://dx.doi.org/10.1016/j.avsg.2019.03.021DOI Listing
November 2019

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

J Magn Reson Imaging 2020 01 17;51(1):205-217. Epub 2019 May 17.

Faculty of Medicine, University of Freiburg, Germany.

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.
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http://dx.doi.org/10.1002/jmri.26782DOI Listing
January 2020

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

Eur Radiol 2019 Oct 15;29(10):5172-5179. Epub 2019 Mar 15.

Institute for Medical Biometry and Statistics, Medical Faculty and Medical Center, University of Freiburg, Freiburg, Germany.

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 mm). 4D flow MRI (spatial/temporal resolution 2 mm/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.
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http://dx.doi.org/10.1007/s00330-019-06104-zDOI Listing
October 2019

Image-based assessment of uncertainty in quantification of carotid lumen.

J Med Imaging (Bellingham) 2018 Jul 24;5(3):034003. Epub 2018 Sep 24.

Fraunhofer MEVIS, Bremen, Germany.

Measurements of the vessel lumen diameter are often used to determine the degree of atherosclerotic disease in carotid arteries. However, quantification results vary with imaging technique and acquisition settings. We aim at providing a tool that quantifies the lumen diameter on different image datasets and gives an estimate of quantification uncertainties, so that they can be taken into consideration when evaluating and comparing measurements. For the segmentation of the vessel lumen, we present an algorithm using ray-casting techniques and partial volume correction. We furthermore propose a scheme for the analysis and exploration of the lumen diameter. Finally, we present a clinically relevant application scenario, in which we explore agreement between lumen diameter estimations in corresponding computed tomography angiography, contrast-enhanced magnetic resonance angiography, time-of-flight, and subtraction images of carotid vessels with severe carotid atherosclerotic plaques.
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http://dx.doi.org/10.1117/1.JMI.5.3.034003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152582PMC
July 2018

Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source.

N Engl J Med 2018 09;379(10):986-7

University of Regensburg, Regensburg, Germany

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http://dx.doi.org/10.1056/NEJMc1809065DOI Listing
September 2018

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

J Cardiovasc Magn Reson 2018 06 21;20(1):43. Epub 2018 Jun 21.

Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.

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 2mm/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 1mm).

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.
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http://dx.doi.org/10.1186/s12968-018-0461-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011486PMC
June 2018

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

J Cardiovasc Magn Reson 2018 06 14;20(1):38. Epub 2018 Jun 14.

Department of Neurology and Neuroscience, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Straße 64, 79106, Freiburg, Germany.

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.
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http://dx.doi.org/10.1186/s12968-018-0456-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001162PMC
June 2018

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

Int J Cardiovasc Imaging 2018 Oct 24;34(10):1629-1636. Epub 2018 May 24.

Department of Neurology and Clinical Neurophysiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

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.
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http://dx.doi.org/10.1007/s10554-018-1369-2DOI Listing
October 2018

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

J Thromb Thrombolysis 2018 Jul;46(1):12-15

Department of Neurology and Clinical Neurophysiology, Medical Center, University of Freiburg, Breisacher Strasse 64, 79106, Freiburg, Germany.

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.
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http://dx.doi.org/10.1007/s11239-018-1658-6DOI Listing
July 2018

Measurement of cardiac valve and aortic blood flow velocities in stroke patients: a comparison of 4D flow MRI and echocardiography.

Int J Cardiovasc Imaging 2018 Jun 11;34(6):939-946. Epub 2018 Jan 11.

Department of Neurology and Clinical Neurophysiology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Straße 64, 79106, Freiburg, Germany.

4D flow MRI is an emerging technique that allows quantification of 3D blood flow in vivo. However, comparisons with methods of blood velocity quantification used in clinical routine are sparse. Therefore, we compared velocity quantification using 4D flow MRI with transthoracic and transesophageal echocardiography at the mitral and aortic valves and the aorta. Forty-eight stroke patients (age 67.3 ± 15.0 years) were examined by 4D flow MRI. Blood flow velocities were assessed using standardized 2D analysis planes positioned in the mitral valve (MV), aortic valve (AV), ascending aorta (AAo), and descending aorta (DAo) and were compared with echocardiography. MRI showed moderate-high correlations of systolic velocity values for the MV (r = 0.67, p < 0.001), AV (r = 0.77, p < 0.001), AAo (r = 0.93, p < 0.001), and DAo (r = 0.76, p < 0.001) along with moderate-high intraclass-correlation-coefficients: MV 0.79 (95% CI 0.62, 0.88), AV 0.86 (95% CI 0.75, 0.92), AAo 0.96 (95% CI 0.93, 0.98), and DAo 0.83 (95% CI 0.70, 0.90). However, MRI underestimated absolute systolic blood flow velocities compared with echocardiography by 8.6% for the MV (p = 0.07), 3.1% for the AV (p = 0.48), 10.7% for the AAo (p = 0.09), and 15.0% for the DAo (p = 0.01). Blood flow velocities obtained using 4D flow MRI and echocardiography at the MV, AV, and the ascending and DAo showed moderate to high correlations. Underestimation of absolute velocity values by MRI was low. Thus, 4D flow MRI seems ideally suited to comprehensively assess cardiac and aortic pathologies and related hemodynamic changes in future studies.
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http://dx.doi.org/10.1007/s10554-018-1298-0DOI Listing
June 2018

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

J Cardiovasc Magn Reson 2017 Sep 6;19(1):67. Epub 2017 Sep 6.

Department of Neurology, Medical Center - University of Freiburg, Breisacher Straße 64, 79106, Freiburg, Germany.

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.
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http://dx.doi.org/10.1186/s12968-017-0379-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586056PMC
September 2017

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

Eur J Radiol 2017 Jun 17;91:148-154. Epub 2017 Apr 17.

Department of Neurology and Neurophysiology, Medical Center, University of Freiburg, Germany.

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=1.15mm). 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.
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http://dx.doi.org/10.1016/j.ejrad.2017.04.011DOI Listing
June 2017

Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany - A national case collection.

Int J Stroke 2017 06 24;12(4):383-391. Epub 2017 Mar 24.

9 Department of Neurology, Klinikum Mittelbaden, Rastatt, Germany.

Background Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran that reverses its anticoagulant effects within minutes. It may exhibit the potential for patients under dabigatran therapy suffering ischemic stroke to regain eligibility for thrombolysis with rt-PA and may inhibit lesion growth in patients with intracerebral hemorrhage on dabigatran. Aims To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of ischemic stroke or intracranial hemorrhage. Methods Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January to August 2016 were used. Results Thirty-one patients presenting with signs of stroke received idarucizumab in 22 stroke centers. Nineteen patients treated with dabigatran presented with ischemic stroke and 12 patients suffered from intracranial bleeding. In patients receiving rt-PA thrombolysis following idarucizumab, 79% benefitted from i.v. thrombolysis with a median improvement of five points in NIHSS. No bleeding complications occurred. Hematoma growth was observed in 2 out of 12 patients with intracranial hemorrhage. The outcome was favorable with a median NIHSS improvement of 5.5 points and mRS 0-3 in 67%. Overall, mortality was low with 6.5% (one patient in each group). Conclusion Administration of rt-PA after reversing dabigatran activity with idarucizumab in case of ischemic stroke is feasible, easy to manage, effective, and appears to be safe. In dabigatran-associated intracranial hemorrhage, idarucizumab has the potential to prevent hematoma growth and improve outcome. Idarucizumab represents a new therapeutic option for patients under dabigatran treatment presenting with ischemic stroke or intracranial hemorrhage.
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http://dx.doi.org/10.1177/1747493017701944DOI Listing
June 2017

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

Stroke 2017 03 8;48(3):671-677. Epub 2017 Feb 8.

From the Department of Neurology (F.S., L.S., T.W., A. Harloff) and Department of Neuroradiology (S.M.), University Medical Centre, Freiburg, Germany; Fraunhofer MEVIS, Bremen, Germany (A. Hennemuth); and Department of Radiology, Feinberg School of Medicine (M.M.) and Department of Biomedical Engineering, McCormick School of Engineering (M.M.), Northwestern University, Chicago, IL.

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 (<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.
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http://dx.doi.org/10.1161/STROKEAHA.116.015102DOI Listing
March 2017

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

Cerebrovasc Dis 2017 4;43(3-4):132-138. Epub 2017 Jan 4.

Department of Neurology, University Medical Center Freiburg, Freiburg, Germany.

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.
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http://dx.doi.org/10.1159/000455053DOI Listing
December 2017

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

J Cardiovasc Magn Reson 2016 05 31;18(1):31. Epub 2016 May 31.

Department of Neurology, University Medical Center Freiburg, Breisacher Straße 64, 79106, Freiburg, Germany.

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.
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http://dx.doi.org/10.1186/s12968-016-0252-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888740PMC
May 2016

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

Cerebrovasc Dis 2015 15;39(5-6):287-92. Epub 2015 Apr 15.

Department of Neurology, University Medical Center Freiburg, Freiburg, Germany.

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.
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http://dx.doi.org/10.1159/000381682DOI Listing
March 2016

In vivo analysis of physiological 3D blood flow of cerebral veins.

Eur Radiol 2015 Aug 1;25(8):2371-80. Epub 2015 Feb 1.

Department of Neurology, University Medical Centre, Breisacherstrasse 64, 79106, Freiburg, Germany,

Objectives: To visualize and quantify physiological blood flow of intracranial veins in vivo using time-resolved, 3D phase-contrast MRI (4D flow MRI), and to test measurement accuracy.

Methods: Fifteen healthy volunteers underwent repeated ECG-triggered 4D flow MRI (3 Tesla, 32-channel head coil). Intracranial venous blood flow was analysed using dedicated software allowing for blood flow visualization and quantification in analysis planes at the superior sagittal, straight, and transverse sinuses. MRI was evaluated for intra- and inter-observer agreement and scan-rescan reproducibility. Measurements of the transverse sinuses were compared with transcranial two-dimensional duplex ultrasound.

Results: Visualization of 3D blood flow within cerebral sinuses was feasible in 100 % and within at least one deep cerebral vein in 87 % of the volunteers. Blood flow velocity/volume increased along the superior sagittal sinus and was lower in the left compared to the right transverse sinus. Intra- and inter-observer reliability and reproducibility of blood flow velocity (mean difference 0.01/0.02/0.02 m/s) and volume (mean difference 0.0002/-0.0003/0.00003 l/s) were good to excellent. High/low velocities were more pronounced (8 % overestimation/9 % underestimation) in MRI compared to ultrasound.

Conclusions: Four-dimensional flow MRI reliably visualizes and quantifies three-dimensional cerebral venous blood flow in vivo and is promising for studies in patients with sinus thrombosis and related diseases.

Key Points: • 4D flow MRI can be used to visualize and quantify physiological cerebral venous haemodynamics • Flow quantification within cerebral sinuses reveals high reliability and accuracy of 4D flow MRI • Blood flow volume and velocity increase along the superior sagittal sinus • Limited spatial resolution currently precludes flow quantification in small cerebral veins.
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http://dx.doi.org/10.1007/s00330-014-3587-xDOI Listing
August 2015

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

Cerebrovasc Dis 2014 3;38(6):410-7. Epub 2014 Dec 3.

Department of Neurology, University Medical Center Freiburg, Freiburg, Germany.

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.
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http://dx.doi.org/10.1159/000369001DOI Listing
September 2015

The great imitator--still today! A case of meningovascular syphilis affecting the posterior circulation.

J Stroke Cerebrovasc Dis 2015 Jan 3;24(1):e1-3. Epub 2014 Oct 3.

Department of Neurology, University Hospital Freiburg, Freiburg, Germany.

Cerebral ischemia due to meningovascular syphilis is rare and more frequently affects the anterior circulation than the posterior circulation. We describe clinical features and imaging studies of a 50-year-old patient with Parinaud syndrome and a syphilitic dorsal midbrain infarction. Brain magnetic resonance imaging indicated vasculitis of the posterior circulation. The diagnosis of meningovascular syphilis was established by serum and cerebrospinal fluid examinations. Although rare, because of the high impact on treatment, clinicians should always be aware of meningovascular syphilis in the differential diagnosis of stroke, particularly in young and male patients with cryptogenic stroke.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.07.046DOI Listing
January 2015

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

Int J Cardiovasc Imaging 2014 Dec 15;30(8):1571-7. Epub 2014 Aug 15.

Department of Neurology, University Medical Center Freiburg, Breisacher Straße 64, 79106, Freiburg, Germany,

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.
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http://dx.doi.org/10.1007/s10554-014-0511-zDOI Listing
December 2014

Letter by Wehrum and Harloff regarding article, "Complex atheromatous plaques in the descending aorta and the risk of stroke: a systematic review and meta-analysis".

Stroke 2014 Aug 19;45(8):e169. Epub 2014 Jun 19.

Department of Neurology, University Medical Center Freiburg, Freiburg, Germany.

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http://dx.doi.org/10.1161/STROKEAHA.114.006211DOI Listing
August 2014