This special issue of Magnetic Resonance in Medical Sciences features the most recent reviews on 4D Flow MRI. These reviews deal with the current status of the emerging technique of 4D Flow MRI facilitated in various areas that are difficult to obtain with conventional flowmetry. MR signals inherently contain flow velocity information. In previous decades, in vivo blood flow measurement was traditionally performed by 2D methods, such as Doppler ultrasonography and 2D phase-contrast MRI, which have long been regarded as mature techniques in hemodynamic flowmetry. Although 2D velocimetries have many advantages over 4D Flow MRI in terms of cost and accessibility, and provide excellent temporal and in-plane spatial resolutions, they also have some disadvantages. The emerging technology of 4D Flow MRI can overcome the shortcomings of conventional 2D imaging. In recent years, hemodynamic analysis has witnessed significant progress that is primarily attributable to advances in 4D Flow MRI.

Cells in the tissues and organs of a living body are subjected to mechanical forces, such as pressure, friction, and tension from their surrounding environment. Cells are equipped with a mechanotransduction mechanism by which they perceive mechanical forces and transmit information into the cell interior, thereby causing physiological or pathogenetic mechano-responses. Endothelial cells (ECs) lining the inner surface of blood vessels are constantly exposed to shear stress caused by blood flow and a cyclic strain caused by intravascular pressure. A number of studies have shown that ECs are sensitive to changes in these hemodynamic forces and alter their morphology and function, sometimes by modifying gene expression. The mechanism of endothelial mechanotransduction has been elucidated, and the plasma membrane has recently been shown to act as a mechanosensor. The lipid order and cholesterol content of plasma membranes change immediately upon the exposure of ECs to hemodynamic forces, resulting in a change in membrane fluidity. These changes in a plasma membrane’s physical properties affect the conformation and function of various ion channels, receptors, and microdomains (such as caveolae and primary cilia), thereby activating a wide variety of downstream signaling pathways. Such endothelial mechanotransduction works to maintain circulatory homeostasis; however, errors in endothelial mechanotransduction can cause abnormalities in vascular physiological function, leading to the initiation and progression of various vascular diseases, such as hypertension, thrombosis, aneurysms, and atherosclerosis. Recent advances in detailed imaging technology and computational fluid dynamics analysis have enabled us to evaluate the hemodynamic forces acting on vascular tissue accurately, contributing greatly to our understanding of vascular mechanotransduction and the pathogenesis of vascular diseases, as well as the development of new therapies for vascular diseases.

Recently, the hemodynamic assessments with 3D cine phase-contrast (PC) MRI (4D flow MRI) have attracted considerable attention from clinicians. Unlike 2D cine PC MRI, the technique allows for cardiac phase-resolved data acquisitions of flow velocity vectors within the entire FOV during a clinically viable period. Thus, the method has enabled retrospective flowmetry in the spatial and temporal axes, which are essential to derive hemodynamic parameters related to vascular homeostasis and those to the progression of the pathologies. Accelerations in imaging are critical for this technology to be clinically viable; however, a high SNR or velocity-to-noise ratio (VNR) is also vital for accurate flow measurements. In this chapter, the technologies enabling this difficult balance are discussed.

In recent years, 4D flow MRI has become increasingly important in clinical applications for the blood vessels in the whole body, heart, and cerebrospinal fluid. 4D flow MRI has advantages over 2D cine phase-contrast (PC) MRI in that any targeted area of interest can be analyzed post-hoc, but there are some factors to be considered, such as ensuring measurement accuracy, a long imaging time and post-processing complexity, and interobserver variability.

Due to the partial volume phenomenon caused by low spatial and temporal resolutions, the accuracy of flow measurement in 4D flow MRI is reduced. For spatial resolution, it is recommended to include at least four voxels in the vessel of interest, and if possible, six voxels. In large vessels such as the aorta, large voxels can be secured and SNR can be maintained, but in small cerebral vessels, SNR is reduced, resulting in reduced accuracy. A temporal resolution of less than 40 ms is recommended. The velocity-to-noise ratio (VNR) of low-velocity blood flow is low, resulting in poor measurement accuracy. The use of dual velocity encoding (VENC) or multi-VENC is recommended to avoid velocity wrap around and to increase VNR. In order to maintain sufficient spatio-temporal resolution, a longer imaging time is required, leading to potential patient movement during examination and a corresponding decrease in measurement accuracy.

For the clinical application of new technologies, including various acceleration techniques, in vitro and in vivo accuracy verification based on existing accuracy-validated 2D cine PC MRI and 4D flow MRI, as well as accuracy verification on the conservation of mass’ principle, should be performed, and intraobserver repeatability, interobserver reproducibility, and test–retest reproducibility should be checked.

Most cardiac diseases cause a non-physiological blood flow pattern known as turbulence around the heart and great vessels, which further worsen the disease itself. However, there is no consensus on how blood flow can be defined in disease conditions. Especially, in the left atrium, the fact that vortex flow already exists makes this debate more complicated. 3D time-resolved phase-contrast (4D flow) MRI is expected to be able to capture blood flow patterns from multiple aspects, such as blood flow velocity, stasis, and vortex quantification. Previous studies have confirmed that physiological vortex flow is predominantly induced by the higher-volume flow from the superior left pulmonary vein. In atrial fibrillation, 4D flow MRI reveals a non-physiological blood flow pattern, which information may add value to well-established clinical risk factors. Currently, the research target of LA analysis has also widened to lung surgeons, pulmonary vein stump thrombosis after left upper lobectomy. 4D flow MRI is expected to be utilized for many more variable diseases that are currently unimaginable.

Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure (PAP). Although right-heart catheterization is the gold standard method for the diagnosis of PH by definition, various less-invasive imaging tests have been used for screening, detection of underlying diseases-causing PH, and monitoring of diseases. Among them, 4D flow MRI is an emerging and unique imaging test that allows for comprehensive visualization of blood flow in the right heart and proximal pulmonary arteries. The characteristic blood flow pattern observed in patients with PH is vortical flow formation in the main pulmonary artery. Recent studies have proposed the use of these findings to determine not only the presence of PH but also estimate the mean PAP. Other applications of 4D flow MRI for PH include measurement of wall shear stress, helicity, and 3D flow balance in the pulmonary arteries. It is worth noting that 4D flow has also the potential for longitudinal follow-ups. In this review, the clinical definition of PH, summary of conventional imaging tests, characteristics of pulmonary arterial flow as shown by 4D flow MRI, and clinical application of 4D flow MRI in the management of patients with PH will be discussed.

4D flow MRI allows time-resolved 3D velocity-encoded phase-contrast imaging for 3D visualization and quantification of aortic and intracardiac flow. Radiologists should be familiar with the principles of 4D flow MRI and methods for evaluating blood flow qualitatively and quantitatively. The most substantial benefits of 4D flow MRI are that it enables the simultaneous comprehensive assessment of different vessels, and that retrospective analysis can be achieved in all vessels in any direction in the field of view, which is especially beneficial for patients with complicated congenital heart disease (CHD). For aortic valvular diseases, new parameters such as wall shear stress and energy loss may provide new prognostic values for 4D flow MRI. In this review, we introduce the clinical applications of 4D flow MRI for the visualization of blood flow and quantification of hemodynamic metrics in the setting of aortic valvular disease and CHD, including intracardiac shunt and coronary artery anomaly.

Despite the recent technical developments, surgery on the thoracic aorta remains challenging and is associated with significant mortality and morbidity. Decisions about when and if to operate are based on a balance between surgical risk and the hazard of aortic rupture. These decisions are sometimes difficult in elective cases of thoracic aortic diseases, including aneurysms and dissections. Abnormal wall stress derived from flow alterations influences disease progression. Therefore, a better understanding of the complex hemodynamic environment inside the aortic lumen will facilitate patient-specific risk assessments of complications, which enable clinicians to provide timely prophylactic interventions. Time-resolved 3D phase-contrast (4D flow) MRI has many advantages for the in vivo assessment of flow dynamics. Recent developments in 4D flow imaging techniques has led to significant advances in our understanding of physiological flow dynamics in healthy subjects and patients with thoracic aortic diseases. In this clinically focused review of thoracic aortic diseases, we demonstrate the clinical advances acquired with 4D flow MRI from published studies. We provide a systematic overview of key evidences and considerations regarding normal thoracic aortas, thoracic aortic aneurysms, aortic dissections, and thoracic aortas with prosthetic graft replacement.

Evaluation of the hemodynamics in the portal venous system plays an essential role in many hepatic pathologies. Changes in portal flow and vessel morphology are often indicative of disease.Routinely used imaging modalities, such as CT, ultrasound, invasive angiography, and MRI, often focus on either hemodynamics or anatomical imaging. In contrast, 4D flow MRI facilitiates a more comprehensive understanding of pathophysiological mechanisms by simultaneously and noninvasively acquiring time-resolved flow and anatomical information in a 3D imaging volume.

Though promising, 4D flow MRI in the portal venous system is especially challenging due to small vessel calibers, slow flow velocities, and breathing motion. In this review article, we will discuss how to account for these challenges when planning and conducting 4D flow MRI acquisitions in the upper abdomen. We will address patient preparation, sequence acquisition, postprocessing, quality control, and analysis of 4D flow data.

In the second part of this article, we will review potential clinical applications of 4D flow MRI in the portal venous system. The most promising area for clinical utilization is the diagnosis and grading of liver cirrhosis and its complications. Relevant parameters acquired by 4D flow MRI include the detection of reduced or reversed flow in the portal venous system, characterization of portosystemic collaterals, and impaired response to a meal challenge. In patients with cirrhosis, 4D flow MRI has the potential to address the major unmet need of noninvasive detection of gastroesophageal varices at high risk for bleeding. This could replace many unnecessary, purely diagnostic, and invasive esophagogastroduodenoscopy procedures, thereby improving patient compliance with follow-up. Moreover, 4D flow MRI offers unique insights and added value for surgical planning and follow-up of multiple hepatic interventions, including transjugular intrahepatic portosystemic shunts, liver transplantation, and hepatic disease in children. Lastly, we will discuss the path to clinical implementation and remaining challenges.

Blood vessels can be regarded as autonomous organs. The endothelial cells on the vessel surface serve as mechanosensors or mechanoreceptors for the flow velocity and turbulence of the blood flow in terms of wall shear stress (WSS), thereby monitoring changes in the flow velocity. Accordingly, the endothelial cells regulate the flow velocity by releasing numerous mediators. Such regulatory systems also trigger atherosclerosis, where the WSS decreases or fluctuates to maintain the flow velocity or local WSS. As occurrences of abdominal aortic aneurysms and aortic dissection are closely related to atherosclerosis, understanding the hemodynamics of the abdominal aorta is necessary to obtain useful information concerning the pathogenesis, diagnosis, and interventions. 4D flow MRI is beneficial for measuring the hemodynamics through comprehensive retrospective flowmetry of the entire spatio-temporal distributions of the flow vectors. This section focuses on abdominal aortic aneurysms and aortic dissection as representative examples of abdominal aortic diseases. Their hemodynamic characteristics and how hemodynamics is involved in their progression are described, and how 4D flow MRI can contribute to their assessment is also explained.

3D cine phase-contrast (4D flow) MRI is a sequence with great potential for non-invasive time-resolved 3D flowmetry at arbitrary vessel sections in various blood vessels. However, it is not widely known that the flowmetry with 4D flow MRI is vulnerable to pulsatile and non-uniform flow. Due to the limited spatial and temporal resolutions, averaging within the 3D voxel is occurring during the flowmetry. A simple solution is to avoid setting the measurement plane in the area where non-uniform flow is dominant, which is possible with an aid of streamline depictions generated by computational fluid dynamics (CFD) or 4D flow MRI data. Unlike 4D flow MRI, flowmetry in CFD simulation can use higher spatial and temporal resolution depending on computer performance; therefore, it is robust to fluctuating non-uniform flow. However, the performance of CFD simulations might be limited due to inlet conditions with low temporal resolution. Difficulty applying complex blood flow such as reflection flow from periphery may also limit accurate simulation. Caution should be taken when comparing the result of CFD simulation to that of 4D flow measurement.

Purpose: To extract the status of hydrocephalus and other cerebrospinal fluid (CSF)-related diseases, a technique to characterize the cardiac- and respiratory-driven CSF motions separately under free breathing was developed. This technique is based on steady-state free precession phase contrast (SSFP-PC) imaging in combination with a Stockwell transform (S-transform).

Methods: 2D SSFP-PC at 3 T was applied to measure the CSF velocity in the caudal-cranial direction within a sagittal slice at the midline (N = 3) under 6-, 10-, and 16-s respiratory cycles and free breathing. The frequency-dependent window width of the S-transform was controlled by a particular scaling factor, which then converted the CSF velocity waveform into a spectrogram. Based on the frequency bands of the cardiac pulsation and respiration, as determined by the electrocardiogram (ECG) and respirator pressure sensors, Gaussian bandpass filters were applied to the CSF spectrogram to extract the time-domain cardiac- and respiratory-driven waveforms.

Results: The cardiac-driven CSF velocity component appeared in the spectrogram clearly under all respiratory conditions. The respiratory-driven velocity under the controlled respiratory cycles was observed as constant frequency signals, compared to a time-varying frequency signal under free breathing. When the widow width was optimized using the scale factor, the temporal change in the respiratory-driven CSF component was even more apparent under free breathing.

Conclusion: Velocity amplitude variations and transient frequency changes of both cardiac- and respiratory-driven components were successfully characterized. These findings indicated that the proposed technique is useful for evaluating CSF motions driven by different cyclic forces.

Blood flow imaging becomes an emerging trend in cardiology with the recent progress in computer technology. It not only visualizes colorful flow velocity streamlines but also quantifies the mechanical stress on cardiovascular structures; thus, it can provide the detailed inspections of the pathophysiology of diseases and predict the prognosis of cardiovascular functions. Clinical applications include the comprehensive assessment of hemodynamics and cardiac functions in echocardiography vector flow mapping (VFM), 4D flow MRI, and surgical planning as a simulation medicine in computational fluid dynamics (CFD).

For evaluation of the hemodynamics, novel mathematically derived parameters obtained using measured velocity distributions are essential. Among them, the traditional and typical parameters are wall shear stress (WSS) and its related parameters. These parameters indicate the mechanical damages to endothelial cells, resulting in degenerative intimal change in vascular diseases. Apart from WSS, there are abundant parameters that describe the strength of the vortical and/or helical flow patterns. For instance, vorticity, enstrophy, and circulation indicate the rotating flow strength or power of 2D vortical flows. In addition, helicity, which is defined as the cross-linking number of the vortex filaments, indicates the 3D helical flow strength and adequately describes the turbulent flow in the aortic root in cases with complicated anatomies. For the description of turbulence caused by the diseased flow, there exist two types of parameters based on completely different concepts, namely: energy loss (EL) and turbulent kinetic energy (TKE). EL is the dissipated energy with blood viscosity and evaluates the cardiac workload related to the prognosis of heart failure. TKE describes the fluctuation in kinetic energy during turbulence, which describes the severity of the diseases that cause jet flow. These parameters are based on intuitive and clear physiological concepts, and are suitable for in vivo flow measurements using inner velocity profiles.