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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.

Pulsatile blood flow through the cavities of the heart and great vessels is time-varying and multidirectional. Access to all regions, phases and directions of cardiovascular flows has formerly been limited. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has enabled more comprehensive access to such flows, with typical spatial resolution of 1.5×1.5×1.5 – 3×3×3 mm 3 , typical temporal resolution of 30–40 ms, and acquisition times in the order of 5 to 25 min. This consensus paper is the work of physicists, physicians and biomedical engineers, active in the development and implementation of 4D Flow CMR, who have repeatedly met to share experience and ideas. The paper aims to assist understanding of acquisition and analysis methods, and their potential clinical applications with a focus on the heart and greater vessels. We describe that 4D Flow CMR can be clinically advantageous because placement of a single acquisition volume is straightforward and enables flow through any plane across it to be calculated retrospectively and with good accuracy. We also specify research and development goals that have yet to be satisfactorily achieved. Derived flow parameters, generally needing further development or validation for clinical use, include measurements of wall shear stress, pressure difference, turbulent kinetic energy, and intracardiac flow components. The dependence of measurement accuracy on acquisition parameters is considered, as are the uses of different visualization strategies for appropriate representation of time-varying multidirectional flow fields. Finally, we offer suggestions for more consistent, user-friendly implementation of 4D Flow CMR acquisition and data handling with a view to multicenter studies and more widespread adoption of the approach in routine clinical investigations.

•Cerebrovascular 5D flow MRI framework is proposed to enable respiratory and cardiac-phase resolved quantification of blood velocity vector fields in the brain.•Cerebrovascular 5D flow MRI facilitates full-field quantification of respiratory flow modulation in complex arterial and venous structures, showing high intra-subject variability in space, which, in parts, can be linked to anatomical structures. 4D flow MRI facilitates quantification of cardiac phase-resolved blood velocity vector fields and has successfully been deployed to study cerebrovascular flow. Besides cardiac-induced flow pulsation, respiration is known to modulate arterial and venous blood flow in the brain. Quantification of the respiratory flow modulation (RFM) holds potential to further our insights into vascular coupling and improve our understanding of cerebral circulation in general. A 5D phase-contrast flow MRI framework was developed to volumetrically quantify RFM by resolving velocity vector fields over the cardiac and respiratory cycle, with high spatial (0.82 mm isotropic) and cardiac (55 ms) resolutions, using two respiratory states whilst accounting for variable physiological RFM delays, with a reasonable acquisition time (20 min at 60 bpm). Recent advances in deep learning-based image reconstruction and analysis methods are incorporated to facilitate the approach. The 5D flow MRI framework was validated in 10 healthy volunteers with reference to fully sampled respiratory-resolved 2D flow MRI orthogonal to the internal carotid artery (ICA), yielding Pearson correlation coefficients of 0.97 and 0.90 and biases of and 0.09 % and 1.77 % for RFM of mean velocity magnitude and amplitude, respectively. The value of cerebrovascular 5D flow MRI is demonstrated using full-field spatially resolved RFM quantification of mean velocity and velocity amplitude, revealing a high physiological intra-subject variability. Cerebrovascular 5D flow MRI enables the study of full-field respiratory flow modulation holding potential of furthering our understanding of cerebral circulation. [Display omitted]

BackgroundDifferent 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.MethodsEight 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.ResultsSW-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.ConclusionsOf 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.

Background Myocardial infarction (MI) leads to complex changes in left ventricular (LV) haemodynamics that are linked to clinical outcomes. We hypothesize that LV blood flow kinetic energy (KE) is altered in MI and is associated with LV function and infarct characteristics. This study aimed to investigate the intra-cavity LV blood flow KE in controls and MI patients, using cardiovascular magnetic resonance (CMR) four-dimensional (4D) flow assessment. Methods Forty-eight patients with MI (acute-22; chronic-26) and 20 age/gender-matched healthy controls underwent CMR which included cines and whole-heart 4D flow. Patients also received late gadolinium enhancement imaging for infarct assessment. LV blood flow KE parameters were indexed to LV end-diastolic volume and include: averaged LV, minimal, systolic, diastolic, peak E-wave and peak A-wave KEi EDV . In addition, we investigated the in-plane proportion of LV KE (%) and the time difference (TD) to peak E-wave KE propagation from base to mid-ventricle was computed. Association of LV blood flow KE parameters to LV function and infarct size were investigated in all groups. Results LV KEi EDV was higher in controls than in MI patients (8.5 ± 3 μJ/ml versus 6.5 ± 3 μJ/ml, P  = 0.02). Additionally, systolic, minimal and diastolic peak E-wave KEi EDV were lower in MI ( P  < 0.05). In logistic-regression analysis, systolic KEi EDV (Beta = − 0.24, P  < 0.01) demonstrated the strongest association with the presence of MI. In multiple-regression analysis, infarct size was most strongly associated with in-plane KE ( r  = 0.5, Beta = 1.1, P  < 0.01). In patients with preserved LV ejection fraction (EF), minimal and in-plane KEi EDV were reduced ( P  < 0.05) and time difference to peak E-wave KE propagation during diastole increased ( P  < 0.05) when compared to controls with normal EF. Conclusions Reduction in LV systolic function results in reduction in systolic flow KEi EDV . Infarct size is independently associated with the proportion of in-plane LV KE. Degree of LV impairment is associated with TD of peak E-wave KE. In patient with preserved EF post MI, LV blood flow KE mapping demonstrated significant changes in the in-plane KE, the minimal KEi EDV and the TD. These three blood flow KE parameters may offer novel methods to identify and describe this patient population.

The purpose of this study was to investigate 3D flow patterns and vessel wall parameters in patients with dilated ascending aorta, age-matched subjects, and healthy volunteers. Thoracic time-resolved 3D phase contrast CMR with 3-directional velocity encoding was applied to 33 patients with dilated ascending aorta (diameter ≥40 mm, age=60±16 years), 15 age-matched normal controls (diameter ≤37 mm, age=68±7.5 years) and 15 young healthy volunteers (diameter ≤30 mm, age=23±2 years). 3D blood flow was visualized and flow patterns were graded regarding presence of supra-physiologic-helix and vortex flow using a semi-quantitative 3-point grading scale. Blood flow velocities, regional wall shear stress (WSS), and oscillatory shear index (OSI) were quantified. Incidence and strength of supra-physiologic-helix and vortex flow in the ascending aorta (AAo) was significantly higher in patients with dilated AAo (16/33 and 31/33, grade 0.9±1.0 and 1.5±0.6) than in controls (2/15 and 7/15, grade 0.2 ± 0.6 and 0.6 ± 0.7, P<.05) or healthy volunteers (1/15 and 0/15, grade 0.1 ± 0.3 P<.05). Greater strength of the ascending aortic helix and vortex flow were associated with significant differences in AAo diameters (P<.05). Peak systolic WSS in the ascending aorta and aortic arch was significantly lower in patients with dilated AAo (P<.0157-.0488). AAo diameter positively correlated to time to peak systolic velocities (r=0.30-0.53, P<.04), OSI (r=0.33-0.49, P<0.02) and inversely correlated to peak systolic WSS (r=0.32-0.40, P<.03). Peak systolic WSS was significantly lower in AAo aneurysms at the right and outer curvature within the AAo and proximal arch (P<.01-.05). Increase in AAo diameter is significantly correlated with the presence and strength of supra-physiologic-helix and vortex formation in the AAo, as well with decrease in systolic WSS and increase in OSI.

Thrombus permeability determines blood flow through the occluding thrombus in acute ischemic stroke (AIS) patients. The quantification of thrombus permeability is challenging since it cannot be directly measured nor derived from radiological imaging data. As a proxy of thrombus permeability, thrombus perviousness has been introduced, which assesses the amount of contrast agent that has penetrated the thrombus on single-phase computed tomography angiography (CTA). We present a method to assess thrombus permeability rather than perviousness. We follow a three-step approach: (1) we propose a theoretical channel-like structure model describing the thrombus morphology. Using Darcy’s law, we provide an analytical description of the permeability for this model. According to the channel-like model, permeability depends on the number of channels in the thrombus, the radius of the occluded artery, and the void fraction representing the volume available for the blood to flow; (2) we measure intra-thrombus blood flow and velocity on dynamic CTA; and (3) we combine the analytical model with the dynamic CTA measurements to estimate thrombus permeability. Analysis of dynamic CTA data from 49 AIS patients showed that the median blood velocity in the thrombus was 0.58 (IQR 0.26–1.35) cm/s. The median flow within the thrombus was 3.48 · 10−3 (IQR 1.71 · 10−3–9.21 · 10−3) ml/s. Thrombus permeability was of the order of 10−3–10−5 mm2, depending on the number of channels in the thrombus. The channel-like thrombus model offers an intuitive way of modelling thrombus permeability, which can be of interest when studying the effect of thrombolytic drugs.

Dynamic positron emission tomography (PET) can be used to non-invasively estimate the blood flow of different organs via compartmental modeling. Out of different PET tracers, water labeled with the radioactive 15 O isotope of oxygen (half-life of 2.04 min) is freely diffusable, and therefore, very well-suited for blood flow quantification. While the earlier 15 O-water PET research has primarily focused on cerebral or myocardial blood flow quantification, the recent emergence of total-body PET scanners has enabled greater application possibilities for both PET imaging in general and also 15 O-water PET based blood flow quantification in particular. However, to validate new methods, it is necessary to compare them to earlier research. To help in this process, we systematically review 53 articles quantifying blood flow via compartmental modeling. We introduce the articles organized within subcategories of cerebral, myocardial, renal, pulmonary, pancreatic, hepatic, muscle, and tumor blood flow and summarize their results so that they can easily be evaluated in terms of population characteristics of the patients such as age or sex ratio and their potential diagnoses. We compare how both the compartment model used and the potential corrections for arterial blood volume, non-perfusable tissue, spill-over from the heart cavities, and time delay caused while the tracer travels between different areas of interest are generally implemented in the articles. We also analyze the differences in the data pre-processing techniques. According to our results, the estimates of cerebral and tumor blood flow vary considerably more between the articles than those of myocardial blood flow. This might be caused by differences in the model approaches or the study populations. We also note that the choice of the unit for these estimates is quite inconsistent as certain researchers seem to prefer mL/min/g over mL/min/mL even if no weight or density parameter is present in the modeling. We encourage more research on sex- and age-based differences in blood flow estimates and organ-specific blood flow quantification studies for kidneys, lungs, liver, and other important organs besides brain and heart.

BackgroundFour-dimensional (4D) flow cardiovascular magnetic resonance (CMR) is feasible for portal blood flow evaluation after placement of transjugular intrahepatic portosystemic shunts (TIPS) in patients with liver cirrhosis. However, clinical acceptance of 4D flow CMR in TIPS patients is limited due to the lack of validation studies. The purpose of this study was to validate 4D flow CMR-derived measurements in TIPS stent grafts using a three-dimensional (3D)-printed flow phantom.MethodsA translucent flow phantom of the portal vasculature was 3D-printed. The phantom consisted of the superior mesenteric vein and the splenic vein draining into the portal vein, the TIPS-tract, and the hepatic vein. A TIPS stent graft (Gore® Viatorr®) was positioned within the TIPS-tract. Superior mesenteric vein and splenic vein served as inlets for blood-mimicking fluid. 4D flow CMR acquisitions were performed at 3T at preset flow rates of 0.8 to 2.8 l/min using velocity encoding of both 1.0 and 2.0 m/s. Flow rates and velocities were measured at predefined levels in the portal vasculature and within the stent graft. Accuracy of 4D flow CMR was assessed through linear regression with reference measurements obtained by flow sensors and two-dimensional (2D) phase contrast (PC) CMR. Intra- and interobserver agreement were assessed through Bland–Altman analyses.ResultsAt a velocity encoding of 2.0 m/s, 4D flow CMR-derived flow rates and velocities showed an excellent correlation with preset flow rates and 2D PC CMR-derived flow velocities at all vascular levels and within the stent graft (all r ≥ 0.958, p ≤ 0.003). At a velocity encoding of 1.0 m/s, aliasing artifacts were present within the stent graft at flow rates ≥ 2.0 l/min. 4D flow CMR-derived measurements revealed high intra- and interobserver agreement.ConclusionsThe in vitro accuracy and precision of 4D flow CMR is unaffected by the presence of TIPS stent grafts, suggesting that 4D flow CMR may be used to monitor TIPS patency in patients with liver cirrhosis.

Cardiovascular magnetic resonance (CMR) evaluation of valvular heart disease is an important diagnostic tool when echocardiography is inconclusive. Phase contrast flow quantification is usually performed during breath hold (BH), which can be challenging in patients suffering from dyspnea and heart failure. The purpose of the present study is to compare a free-breathing (FB) with the conventional BH approach for flow quantification in the aortic, pulmonary and tricuspid valves in 20 healthy subjects (HS) and 25 patients with tricuspid regurgitation (TR). Aortic (AoFF) and pulmonary forward flow volume (PuFF), and tricuspid inflow volume (TrIF) were evaluated. Mean, standard deviation (SD) and limits of agreement (LoA) were calculated. There were good agreements between phase contrast flow volumes obtained by FB and BH approach. Mean difference ± SD / LoA for AoFF during BH versus FB were 1 ± 6 / -10 to 13 ml. The corresponding for PuFF were 1 ± 6 / -11 to 13 ml, and for TrIF − 3 ± 6 / -15 to 9 ml, respectively. Thus, free-breathing CMR flow acquisition can be an important alternative in the assessment of stroke volume, valvular regurgitant volume and be useful in all patients with difficulties to hold their breath.