Repeatability and reproducibility of various 4D Flow MRI postprocessing software programs in a multi-software and multi-vendor cross-over comparison study.

BACKGROUND: Different software programs are available for the evaluation of 4D Flow cardiovascular magnetic resonance (CMR). A good agreement of the results between programs is a prerequisite for the acceptance of the method. Therefore, the goal was to compare quantitative results from a cross-over comparison in individuals examined on two scanners of different vendors analyzed with four postprocessing software packages. METHODS: Eight healthy subjects (27 ± 3 years, 3 women) were each examined on two 3T CMR systems (Ingenia, Philips Healthcare; MAGNETOM Skyra, Siemens Healthineers) with a standardized 4D Flow CMR sequence. Six manually placed aortic contours were evaluated with Caas (Pie Medical Imaging, SW-A), cvi42 (Circle Cardiovascular Imaging, SW-B), GTFlow (GyroTools, SW-C), and MevisFlow (Fraunhofer Institute MEVIS, SW-D) to analyze seven clinically used parameters including stroke volume, peak flow, peak velocity, and area as well as typically scientifically used wall shear stress values. Statistical analysis of inter- and intrareader variability, inter-software and inter-scanner comparison included calculation of absolute and relative error (ER), intraclass correlation coefficient (ICC), Bland-Altman analysis, and equivalence testing based on the assumption that inter-software differences needed to be within 80% of the range of intrareader differences. RESULTS: SW-A and SW-C were the only software programs showing agreement for stroke volume (ICC = 0.96; ER = 3 ± 8%), peak flow (ICC: 0.97; ER = -1 ± 7%), and area (ICC = 0.81; ER = 2 ± 22%). Results from SW-A/D and SW-C/D were equivalent only for area and peak flow. Other software pairs did not yield equivalent results for routinely used clinical parameters. Especially peak maximum velocity yielded poor agreement (ICC ≤ 0.4) between all software packages except SW-A/D that showed good agreement (ICC = 0.80). Inter- and intrareader consistency for clinically used parameters was best for SW-A and SW-D (ICC = 0.56-97) and worst for SW-B (ICC = -0.01-0.71). Of note, inter-scanner differences per individual tended to be smaller than inter-software differences. CONCLUSIONS: Of all tested software programs, only SW-A and SW-C can be used equivalently for determination of stroke volume, peak flow, and vessel area. Irrespective of the applied software and scanner, high intra- and interreader variability for all parameters have to be taken into account before introducing 4D Flow CMR in clinical routine. Especially in multicenter clinical trials a single image evaluation software should be applied.

4D Flow cardiovascular magnetic resonance consensus statement: 2023 update.

Hemodynamic assessment is an integral part of the diagnosis and management of cardiovascular disease. Four-dimensional cardiovascular magnetic resonance flow imaging (4D Flow CMR) allows comprehensive and accurate assessment of flow in a single acquisition. This consensus paper is an update from the 2015 '4D Flow CMR Consensus Statement'. We elaborate on 4D Flow CMR sequence options and imaging considerations. The document aims to assist centers starting out with 4D Flow CMR of the heart and great vessels with advice on acquisition parameters, post-processing workflows and integration into clinical practice. Furthermore, we define minimum quality assurance and validation standards for clinical centers. We also address the challenges faced in quality assurance and validation in the research setting. We also include a checklist for recommended publication standards, specifically for 4D Flow CMR. Finally, we discuss the current limitations and the future of 4D Flow CMR. This updated consensus paper will further facilitate widespread adoption of 4D Flow CMR in the clinical workflow across the globe and aid consistently high-quality publication standards.

CARDIOKIN1: Computational Assessment of Myocardial Metabolic Capability in Healthy Controls and Patients With Valve Diseases.

BACKGROUND: Many heart diseases can result in reduced pumping capacity of the heart muscle. A mismatch between ATP demand and ATP production of cardiomyocytes is one of the possible causes. Assessment of the relation between myocardial ATP production (MVATP) and cardiac workload is important for better understanding disease development and choice of nutritional or pharmacologic treatment strategies. Because there is no method for measuring MVATP in vivo, the use of physiology-based metabolic models in conjunction with protein abundance data is an attractive approach. METHOD: We developed a comprehensive kinetic model of cardiac energy metabolism (CARDIOKIN1) that recapitulates numerous experimental findings on cardiac metabolism obtained with isolated cardiomyocytes, perfused animal hearts, and in vivo studies with humans. We used the model to assess the energy status of the left ventricle of healthy participants and patients with aortic stenosis and mitral valve insufficiency. Maximal enzyme activities were individually scaled by means of protein abundances in left ventricle tissue samples. The energy status of the left ventricle was quantified by the ATP consumption at rest (MVATP[rest]), at maximal workload (MVATP[max]), and by the myocardial ATP production reserve, representing the span between MVATP(rest) and MVATP(max). RESULTS: Compared with controls, in both groups of patients, MVATP(rest) was increased and MVATP(max) was decreased, resulting in a decreased myocardial ATP production reserve, although all patients had preserved ejection fraction. The variance of the energetic status was high, ranging from decreased to normal values. In both patient groups, the energetic status was tightly associated with mechanic energy demand. A decrease of MVATP(max) was associated with a decrease of the cardiac output, indicating that cardiac functionality and energetic performance of the ventricle are closely coupled. CONCLUSIONS: Our analysis suggests that the ATP-producing capacity of the left ventricle of patients with valvular dysfunction is generally diminished and correlates positively with mechanical energy demand and cardiac output. However, large differences exist in the energetic state of the myocardium even in patients with similar clinical or image-based markers of hypertrophy and pump function. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03172338 and NCT04068740.

Virtual reality in cardiac interventions-New tools or new toys?

Improvementsin medical imaging and a steady increase in computing power are leading to new possibilities in the field of cardiovascular interventions. Interventions can be planned in advance in greater detail, even to the point of simulating procedures. Nevertheless, all techniques are at an early stage of development. It is of utmost importance that tools, especially if they can be used as decision support are intensively validated and their accuracy is demonstrated. In our commentary, we summarize current techniques for impprovements in planning and guiding of procedures, but also critically discuss the downsides of these techniques. Following the work of Kenichi and colleagues, we also discuss necessary steps in advancing new tools and techniques, particularly as they are used in routine clinical practice. We also discuss the role of artificial intelligence, which could play a crucial role in this context in the future.

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.

Analysis of three-chamber view conventional and tagged cine MRI in patients with suspected hypertrophic cardiomyopathy.

OBJECTIVES: To investigate the potential value of adding a tagged three-chamber (3Ch) cine to clinical hypertrophic cardiomyopathy (HCM) magnetic resonance imaging (MRI) protocols, including to help distinguish HCM patients with regionally impaired cardiac function. METHODS: Forty-eight HCM patients, five patients with "septal knuckle" (SK), and 20 healthy volunteers underwent MRI at 1.5T; a tagged 3Ch cine was added to the protocol. Regional strain, myocardial wall thickness, and mitral valve leaflet lengths were measured in the 3Ch view. RESULTS: In HCM, we found a reduced tangential strain with decreased diastolic relaxation in both hypertrophied (p = 0.003) and remote segments (p = 0.035). Strain in the basal septum correlated with the length of the coaptation zone + residual leaflet (r = 0.48, p < 0.001). In the basal free wall, patients with SK had faster relaxation compared to HCM patients with septal hypertrophy. DISCUSSION: The 3Ch tagged MRI sequence provides useful information for the examination of suspected HCM patients, with minimal additional time cost. Local wall function is closely associated with morphological changes of the mitral apparatus measured in the same plane and may provide insights into mechanisms of obstruction. The additional strain information may be helpful when analyzing local myocardial wall motion patterns in the presence of SK.

Elevated diastolic wall shear stress in regurgitant semilunar valvular lesions.

BACKGROUND: Alterations in wall shear stress (WSS) assessed using 4D flow MRI have been shown to play a role in various vascular pathologies, such as bicuspid aortic valve aortopathy. Most studies have focused on systolic WSS, whereas altered diastolic hemodynamics in regurgitant semilunar valvular lesions have not so far been well characterized. PURPOSE: To investigate diastolic WSS in aortic and pulmonary regurgitation. STUDY TYPE: Retrospective data analysis. POPULATION: Thirty tetralogy of Fallot patients, 19 bicuspid aortic valve patients, 11 healthy volunteers. FIELD STRENGTH/SEQUENCE: 5 T, 3D time-resolved phase-contrast MRI with 3D velocity encoding. ASSESSMENT: Estimation of WSS and its axial and circumferential vector components along cardiac cycle timeframes in the proximal main pulmonary artery in pulmonary regurgitation (PR) and in the proximal ascending aorta in aortic regurgitation (AR) as well as in healthy volunteers. STATISTICAL TESTS: Wilcoxon matched pairs test was used for intra-group comparisons and Mann-Whitney test for intergroup comparisons. Correlations were assessed using Spearman correlation. RESULTS: WSS along the entire cardiac cycle was higher in PR and AR in comparison with controls (mean WSS 0.381 ± 0.070 vs. 0.220 ± 0.018, P < 0.0001; 0.361 ± 0.099 vs. 0.212 ± 0.030, P < 0.0001; respectively). Peak diastolic WSS was significantly higher than the mean WSS in AR and PR (P < 0.0001-0.005). The severity of PR correlated with the peak diastolic axial WSS (Spearman's r s = 0.454, P = 0.018), whereas the severity of AR correlated with both peak systolic and diastolic tangential WSS (Spearman's r s = 0.458, P = 0.049; r s = 0.539, P = 0.017, respectively). DATA CONCLUSION: Elevated diastolic WSS is a component of the altered flow hemodynamics in AR and PR. This may give more insight into the pathophysiologic role of WSS in vascular remodeling in AR and PR. LEVEL OF EVIDENCE: 4 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:763-770.

Patient-specific requirements and clinical validation of MRI-based pressure mapping: A two-center study in patients with aortic coarctation.

BACKGROUND: Invasive peak-to-peak pressure gradients are the current clinical reference standard for assessing aortic coarctation. To obtain them, patients need to undergo arterial heart catheterization. Unless an intervention is performed, the procedure remains purely diagnostic, while the concomitant risks remain. PURPOSE: To validate MRI-based pressure mapping against pressure drop derived from heart catheterization and to define minimal clinical requirements. STUDY TYPE: Prospective clinical validation study. POPULATION: Twenty-seven coarctation patients with an indicated heart catheterization were enrolled at two clinical centers. MRI SEQUENCES: 1.5T including 4D velocity-encoded MRI and 3D anatomical imaging of the aorta. ASSESSMENT: Pressure drop across the stenosis was calculated by pressure mapping based on the pressure Poisson equation. Calculated pressure drops were compared with catheter measured data. Spatial and temporal resolution were analyzed using in silico phantom-based data as well as in vivo measurements. STATISTICS: Pressure drop was compared to peak-to-peak measurements. A two-sample paired mean equivalence test was used. RESULTS: In patients without imaging artifacts and a required spatial resolution ≥5 voxel/diameter, significant equivalence of pressure mapping compared to heart catheterization was found (17.5 ± 6.49 vs. 16.6 ± 6.53 mmHg, P < 0.001). DATA CONCLUSION: Pressure mapping provides equivalent accuracy to pressure drop obtained from heart catheterization in patients 1) without previous stenting and 2) with sufficient spatial image resolution (at least 5 voxels/diameter). In these patients the method can reliably be performed prior to the actual procedure, and thus allows safe noninvasive treatment planning based on MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:81-89.

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.

Wall shear stress estimation in the aorta: Impact of wall motion, spatiotemporal resolution, and phase noise.

BACKGROUND: Wall shear stress (WSS) presents an important parameter for assessing blood flow characteristics and evaluating flow-mediated lesions in the aorta. PURPOSE: To investigate the robustness of WSS and oscillatory shear index (OSI) estimation based on 4D flow MRI against vessel wall motion, spatiotemporal resolution, and velocity encoding (VENC). STUDY TYPE: Simulated and prospective. POPULATION: Synthetic 4D flow MRI data of the aorta, simulated using the Lattice-Boltzmann method; in vivo 4D flow MRI data of the aorta from healthy volunteers (n = 11) and patients with congenital heart defects (n = 17). FIELD STRENGTH/SEQUENCE: 1.5T; 4D flow MRI with PEAK-GRAPPA acceleration and prospective electrocardiogram triggering. ASSESSMENT: Predicated upon 3D cubic B-splines interpolation of the image velocity field, WSS was estimated in mid-systole, early-diastole, and late-diastole and OSI was derived. We assessed the impact of spatiotemporal resolution and phase noise, and compared results based on tracked-using deformable registration-and static vessel wall location. STATISTICAL TESTS: Bland-Altman analysis to assess WSS/OSI differences; Hausdorff distance (HD) to assess wall motion; and Pearson's correlation coefficient (PCC) to assess correlation of HD with WSS. RESULTS: Synthetic data results show systematic over-/underestimation of WSS when different spatial resolution (mean ± 1.96 SD up to -0.24 ± 0.40 N/m2 and 0.5 ± 1.38 N/m2 for 8-fold and 27-fold voxel size, respectively) and VENC-depending phase noise (mean ± 1.96 SD up to 0.31 ± 0.12 N/m2 and 0.94 ± 0.28 N/m2 for 2-fold and 4-fold VENC increase, respectively) are given. Neglecting wall motion when defining the vessel wall perturbs WSS estimates to a considerable extent (1.96 SD up to 1.21 N/m2 ) without systematic over-/underestimation (Bland-Altman mean range -0.06 to 0.05). DATA CONCLUSION: In addition to sufficient spatial resolution and velocity to noise ratio, accurate tracking of the vessel wall is essential for reliable image-based WSS estimation and should not be neglected if wall motion is present. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

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.

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.

MRI-based computational hemodynamics in patients with aortic coarctation using the lattice Boltzmann methods: Clinical validation study.

PURPOSE: To introduce a scheme based on a recent technique in computational hemodynamics, known as the lattice Boltzmann methods (LBM), to noninvasively measure pressure gradients in patients with a coarctation of the aorta (CoA). To provide evidence on the accuracy of the proposed scheme, the computed pressure drop values are compared against those obtained using the reference standard method of catheterization. MATERIALS AND METHODS: Pre- and posttreatment LBM-based pressure gradients for 12 patients with CoA were simulated for the time point of peak systole using the open source library OpenLB. Four-dimensional (4D) flow-sensitive phase-contrast MRI at 1.5 Tesla was used to acquire flow and to setup the simulation. The vascular geometry was reconstructed using 3D whole-heart MRI. Patients underwent pre- and postinterventional pressure catheterization as a reference standard. RESULTS: There is a significant linear correlation between the pretreatment catheter pressure drops and those computed based on the LBM simulation, r=.85, P<.001. The bias was -0.58 ± 4.1 mmHg and was not significant ( P=0.64) with a 95% confidence interval (CI) of -3.22 to 2.06. For the posttreatment results, the bias was larger and at -2.54 ± 3.53 mmHg with a 95% CI of -0.17 to -4.91 mmHg. CONCLUSION: The results indicate a reasonable agreement between the simulation results and the catheter measurements. LBM-based computational hemodynamics can be considered as an alternative to more traditional computational fluid dynamics schemes for noninvasive pressure calculations and can assist in diagnosis and therapy planning. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:139-146.

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.

Analyzing myocardial torsion based on tissue phase mapping cardiovascular magnetic resonance.

BACKGROUND: The purpose of this work is to analyze differences in left ventricular torsion between volunteers and patients with non-ischemic cardiomyopathy based on tissue phase mapping (TPM) cardiovascular magnetic resonance (CMR). METHODS: TPM was performed on 27 patients with non-ischemic cardiomyopathy and 14 normal volunteers. Patients underwent a standard CMR including late gadolinium enhancement (LGE) for the assessment of myocardial scar and ECG-gated cine CMR for global cardiac function. TPM was acquired in short-axis orientation at base, mid, and apex for all subjects. After evaluation by experienced observers, the patients were divided in subgroups according to the presence or absence of LGE (LGE+/LGE-), local wall motion abnormalities (WM+/WM-), and having a preserved (≥50%) or reduced (<50%) ejection fraction (EF+/EF-). TPM data was semi-automatically segmented and global LV torsion was computed for each cardiac time frame for endocardial and epicardial layers, and for the entire myocardium. RESULTS: Maximum myocardial torsion was significantly lower for patients with reduced EF compared to controls (0.21 ± 0.15°/mm vs. 0.36 ± 0.11°/mm, p = 0.018), but also for patients with wall motion abnormalities (0.21 ± 0.13°/mm vs. 0.36 ± 0.11°/mm, p = 0.004). Global myocardial torsion showed a positive correlation (r = 0.54, p < 0.001) with EF. Moreover, endocardial torsion was significantly higher than epicardial torsion for EF+ subjects (0.56 ± 0.33°/mm vs. 0.34 ± 0.18°/mm, p = 0.039) and for volunteers (0.46 ± 0.16°/mm vs. 0.30 ± 0.09°/mm, p = 0.004). The difference in maximum torsion between endo- and epicardial layers was positively correlated with EF (r = 0.47, p = 0.002) and age (r = 0.37, p = 0.016) for all subjects. CONCLUSIONS: TPM can be used to detect significant differences in LV torsion in patients with reduced EF and in the presence of local wall motion abnormalities. We were able to quantify torsion differences between the endocardium and epicardium, which vary between patient subgroups and are correlated to age and EF.

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.

MRI-based computational fluid dynamics for diagnosis and treatment prediction: clinical validation study in patients with coarctation of aorta.

PURPOSE: To reduce the need for diagnostic catheterization and optimize treatment in a variety of congenital heart diseases, magnetic resonance imaging (MRI)-based computational fluid dynamics (CFD) is proposed. However, data about the accuracy of CFD in a clinical context are still sparse. To fill this gap, this study compares MRI-based CFD to catheterization in the coarctation of aorta (CoA) setting. MATERIALS AND METHODS: Thirteen patients with CoA were investigated by routine MRI prior to catheterization. 3D whole-heart MRI was used to reconstruct geometries and 4D flow-sensitive phase-contrast MRI was used to acquire flows. Peak systolic flows were simulated using the program FLUENT. RESULTS: Peak systolic pressure drops in CoA measured by catheterization and CFD correlated significantly for both pre- and posttreatment measurements (pre: r = 0.98, p = 0.00; post: r = 0.87, p = 0.00). The pretreatment bias was -0.5 ± 3.33 mmHg (95% confidence interval -2.55 to 1.47 mmHg). CFD predicted a reduction of the peak systolic pressure drop after treatment that ranged from 17.6 ± 5.56 mmHg to 6.7 ± 5.58 mmHg. The posttreatment bias was 3.0 ± 2.91 mmHg (95% CI -1.74 to 5.43 mmHg). CONCLUSION: Peak systolic pressure drops can be reliably calculated using MRI-based CFD in a clinical setting. Therefore, CFD might be an attractive noninvasive alternative to diagnostic catheterization.

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

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.