Unraveling diurnal and technical variability in cerebral hemodynamics from neurovascular 4D-Flow MRI.

Neurovascular 4D-Flow MRI enables non-invasive evaluation of cerebral hemodynamics including measures of cerebral blood flow (CBF), vessel pulsatility index (PI), and cerebral pulse wave velocity (PWV). 4D-Flow measures have been linked to various neurovascular disorders including small vessel disease and Alzheimer's disease; however, physiological and technical sources of variability are not well established. Here, we characterized sources of diurnal physiological and technical variability in cerebral hemodynamics using 4D-Flow in a retrospective study of cognitively unimpaired older adults (N = 750) and a prospective study of younger adults (N = 10). Younger participants underwent repeated MRI sessions at 7am, 4 pm, and 10 pm. In the older cohort, having an MRI earlier on the day was significantly associated with higher CBF and lower PI. In prospective experiments, time of day significantly explained variability in CBF and PI; however, not in PWV. Test-retest experiments showed high CBF intra-session repeatability (repeatability coefficient (RPC) =7.2%), compared to lower diurnal repeatability (RPC = 40%). PI and PWV displayed similar intra-session and diurnal variability (PI intra-session RPC = 22%, RPC = 24% 7am vs 4 pm; PWV intra-session RPC = 17%, RPC = 21% 7am vs 4 pm). Overall, CBF measures showed low technical variability, supporting diurnal variability is from physiology. PI and PWV showed higher technical variability but less diurnal variability.

Four-Dimensional Flow MR Imaging: Technique and Advances.

4D Flow MRI is an advanced imaging technique for comprehensive non-invasive assessment of the cardiovascular system. The capture of the blood velocity vector field throughout the cardiac cycle enables measures of flow, pulse wave velocity, kinetic energy, wall shear stress, and more. Advances in hardware, MRI data acquisition and reconstruction methodology allow for clinically feasible scan times. The availability of 4D Flow analysis packages allows for more widespread use in research and the clinic and will facilitate much needed multi-center, multi-vendor studies in order to establish consistency across scanner platforms and to enable larger scale studies to demonstrate clinical value.

Focused Abbreviated Survey MRI Protocols for Brain and Spine Imaging.

There has been extensive growth in both the technical development and the clinical applications of MRI, establishing this modality as one of the most powerful diagnostic imaging tools. However, long examination and image interpretation times still limit the application of MRI, especially in emergent clinical settings. Rapid and abbreviated MRI protocols have been developed as alternatives to standard MRI, with reduced imaging times, and in some cases limited numbers of sequences, to more efficiently answer specific clinical questions. A group of rapid MRI protocols used at the authors' institution, referred to as FAST (focused abbreviated survey techniques), are designed to include or exclude emergent or urgent conditions or screen for specific entities. These FAST protocols provide adequate diagnostic image quality with use of accelerated approaches to produce imaging studies faster than traditional methods. FAST protocols have become critical diagnostic screening tools at the authors' institution, allowing confident and efficient confirmation or exclusion of actionable findings. The techniques commonly used to reduce imaging times, the imaging protocols used at the authors' institution, and future directions in FAST imaging are reviewed to provide a practical and comprehensive overview of FAST MRI for practicing neuroradiologists. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Reduced basal macrovascular and microvascular cerebral blood flow in young adults with metabolic syndrome: potential mechanisms.

Ninety-million Americans suffer metabolic syndrome (MetSyn), increasing the risk of diabetes and poor brain outcomes, including neuropathology linked to lower cerebral blood flow (CBF), predominantly in anterior regions. We tested the hypothesis that total and regional CBF is lower in MetSyn more so in the anterior brain and explored three potential mechanisms. Thirty-four controls (25 ± 5 yr) and 19 MetSyn (30 ± 9 yr), with no history of cardiovascular disease/medications, underwent four-dimensional flow magnetic resonance imaging (MRI) to quantify macrovascular CBF, whereas arterial spin labeling quantified brain perfusion in a subset (n = 38/53). Contributions of cyclooxygenase (COX; n = 14), nitric oxide synthase (NOS, n = 17), or endothelin receptor A signaling (n = 13) were tested with indomethacin, NG-monomethyl-L-arginine (L-NMMA), and Ambrisentan, respectively. Total CBF was 20 ± 16% lower in MetSyn (725 ± 116 vs. 582 ± 119 mL/min, P < 0.001). Anterior and posterior brain regions were 17 ± 18% and 30 ± 24% lower in MetSyn; reductions were not different between regions (P = 0.112). Global perfusion was 16 ± 14% lower in MetSyn (44 ± 7 vs. 36 ± 5 mL/100 g/min, P = 0.002) and regionally in frontal, occipital, parietal, and temporal lobes (range 15-22%). The decrease in CBF with L-NMMA (P = 0.004) was not different between groups (P = 0.244, n = 14, 3), and Ambrisentan had no effect on either group (P = 0.165, n = 9, 4). Interestingly, indomethacin reduced CBF more in Controls in the anterior brain (P = 0.041), but CBF decrease in posterior was not different between groups (P = 0.151, n = 8, 6). These data indicate that adults with MetSyn exhibit substantially reduced brain perfusion without regional differences. Moreover, this reduction is not due to loss of NOS or gain of ET-1 signaling but rather a loss of COX vasodilation.NEW & NOTEWORTHY We tested the impact of insulin resistance (IR) on resting cerebral blood flow (CBF) in adults with metabolic syndrome (MetSyn). Using MRI and research pharmaceuticals to study the role of NOS, ET-1, or COX signaling, we found that adults with MetSyn exhibit substantially lower CBF that is not explained by changes in NOS or ET-1 signaling. Interestingly, adults with MetSyn show a loss of COX-mediated vasodilation in the anterior but not posterior circulation.

Reference values for 4D flow magnetic resonance imaging of the portal venous system.

PURPOSE: The purpose of this work was to establish normal reference values for 4D flow MRI-derived flow, velocity, and vessel diameters, and to define characteristic flow patterns in the portal venous system of healthy adult subjects. METHODS: For this retrospective study, we screened all available 4D flow MRI exams of the upper abdomen in healthy adults acquired at our institution between 2012 and 2022 at either 1.5 T or 3.0 T MRI after ≥ 5 h fasting. Flow, velocity, and effective diameter were quantified in the 8 planes in the portal venous system (splenic vein, superior mesenteric vein, main, right, and left portal veins). Vessel delineation was manually adjusted over time. Reference ranges for were defined as the mean ± 2 standard deviations. Three readers noted helical and vortical flow on time-resolved pathline visualizations. Conservation of mass flow analysis was performed for quality assurance. RESULTS: We included 44 healthy subjects (26 female, 18-74 years) in the analysis. We report reference values for mean and peak flow, mean velocity, and vessel diameter in the healthy portal vein using 4D flow MRI. Normal flow patterns in the portal vein included faint helical (66%) or linear flow (34%). Conservation of mass analysis demonstrated a relative error of 1.1 ± 4.6% standard deviation (SD) at the splenomesenteric confluence and - 1.4 ± 4.1% SD at the portal bifurcation. CONCLUSION: We have reported normal hemodynamic values that are necessary baseline data for emerging clinical applications of 4D flow MRI in the portal venous system. Results are consistent with previously published values from smaller cohorts.

Normative Cerebral Hemodynamics in Middle-aged and Older Adults Using 4D Flow MRI: Initial Analysis of Vascular Aging.

Background Characterizing cerebrovascular hemodynamics in older adults is important for identifying disease and understanding normal neurovascular aging. Four-dimensional (4D) flow MRI allows for a comprehensive assessment of cerebral hemodynamics in a single acquisition. Purpose To establish reference intracranial blood flow and pulsatility index values in a large cross-sectional sample of middle-aged (45-65 years) and older (>65 years) adults and characterize the effect of age and sex on blood flow and pulsatility. Materials and Methods In this retrospective study, patients aged 45-93 years (cognitively unimpaired) underwent cranial 4D flow MRI between March 2010 and March 2020. Blood flow rates and pulsatility indexes from 13 major arteries and four venous sinuses and total cerebral blood flow were collected. Intraobserver and interobserver reproducibility of flow and pulsatility measures was assessed in 30 patients. Descriptive statistics (mean ± SD) of blood flow and pulsatility were tabulated for the entire group and by age and sex. Multiple linear regression and linear mixed-effects models were used to assess the effect of age and sex on total cerebral blood flow and vessel-specific flow and pulsatility, respectively. Results There were 759 patients (mean age, 65 years ± 8 [SD]; 506 female patients) analyzed. For intra- and interobserver reproducibility, median intraclass correlation coefficients were greater than 0.90 for flow and pulsatility measures across all vessels. Regression coefficients ß ± standard error from multiple linear regression showed a 4 mL/min decrease in total cerebral blood flow each year (age ß = -3.94 mL/min per year ± 0.44; P < .001). Mixed effects showed a 1 mL/min average annual decrease in blood flow (age ß = -0.95 mL/min per year ± 0.16; P < .001) and 0.01 arbitrary unit (au) average annual increase in pulsatility over all vessels (age ß = 0.011 au per year ± 0.001; P < .001). No evidence of sex differences was observed for flow (ß = -1.60 mL/min per male patient ± 1.77; P = .37), but pulsatility was higher in female patients (sex ß = -0.018 au per male patient ± 0.008; P = .02). Conclusion Normal reference values for blood flow and pulsatility obtained using four-dimensional flow MRI showed correlations with age. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Steinman in this issue.

Vascular contributions to Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia and is characterized by progressive neurodegeneration and cognitive decline. Understanding the pathophysiology underlying AD is paramount for the management of individuals at risk of and suffering from AD. The vascular hypothesis stipulates a relationship between cardiovascular disease and AD-related changes although the nature of this relationship remains unknown. In this review, we discuss several potential pathological pathways of vascular involvement in AD that have been described including dysregulation of neurovascular coupling, disruption of the blood brain barrier, and reduced clearance of metabolite waste such as beta-amyloid, a toxic peptide considered the hallmark of AD. We will also discuss the two-hit hypothesis which proposes a 2-step positive feedback loop in which microvascular insults precede the accumulation of Aß and are thought to be at the origin of the disease development. At neuroimaging, signs of vascular dysfunction such as chronic cerebral hypoperfusion have been demonstrated, appearing early in AD, even before cognitive decline and alteration of traditional biomarkers. Cerebral small vessel disease such as cerebral amyloid angiopathy, characterized by the aggregation of Aß in the vessel wall, is highly prevalent in vascular dementia and AD patients. Current data is unclear whether cardiovascular disease causes, precipitates, amplifies, precedes, or simply coincides with AD. Targeted imaging tools to quantitatively evaluate the intracranial vasculature and longitudinal studies in individuals at risk for or in the early stages of the AD continuum could be critical in disentangling this complex relationship between vascular disease and AD.

Automated hemodynamic assessment for cranial 4D flow MRI.

Cranial 4D flow MRI post-processing typically involves manual user interaction which is time-consuming and associated with poor repeatability. The primary goal of this study is to develop a robust quantitative velocity tool (QVT) that utilizes threshold-based segmentation techniques to improve segmentation quality over prior approaches based on centerline processing schemes (CPS) that utilize k-means clustering segmentation. This tool also includes an interactive 3D display designed for simplified vessel selection and automated hemodynamic visualization and quantification. The performances of QVT and CPS were compared in vitro in a flow phantom and in vivo in 10 healthy participants. Vessel segmentations were compared with ground-truth computed tomography in vitro (29 locations) and manual segmentation in vivo (13 locations) using linear regression. Additionally, QVT and CPS MRI flow rates were compared to perivascular ultrasound flow in vitro using linear regression. To assess internal consistency of flow measures in vivo, conservation of flow was assessed at vessel junctions using linear regression and consistency of flow along vessel segments was analyzed by fitting a Gaussian distribution to a histogram of normalized flow values. Post-processing times were compared between the QVT and CPS using paired t-tests. Vessel areas segmented in vitro (CPS: slope = 0.71, r = 0.95 and QVT: slope = 1.03, r = 0.95) and in vivo (CPS: slope = 0.61, r = 0.96 and QVT: slope = 0.93, r = 0.96) were strongly correlated with ground-truth area measurements. However, CPS (using k-means segmentation) consistently underestimated vessel areas. Strong correlations were observed between QVT and ultrasound flow (slope = 0.98, r = 0.96) as well as flow at junctions (slope = 1.05, r = 0.98). Mean and standard deviation of flow along vessel segments was 9.33e-16 ± 3.05%. Additionally, the QVT demonstrated excellent interobserver agreement and significantly reduced post-processing by nearly 10 min (p < 0.001). By completely automating post-processing and providing an easy-to-use 3D visualization interface for interactive vessel selection and hemodynamic quantification, the QVT offers an efficient, robust, and repeatable means to analyze cranial 4D flow MRI. This software is freely available at: https://github.com/uwmri/QVT.

Clinical Applications of 4D Flow MRI in the Portal Venous System.

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.

Non-invasive assessment of mesenteric hemodynamics in patients with suspected chronic mesenteric ischemia using 4D flow MRI.

PURPOSE: Chronic mesenteric ischemia (CMI) is a rare disease with a particularly difficult diagnosis. In this study, 4D flow MRI is used to quantitatively evaluate mesenteric hemodynamics before and after a meal in patients suspected of having CMI and healthy individuals. METHODS: Nineteen patients suspected of CMI and twenty control subjects were analyzed. Subjects were scanned using a radially undersampled 4D flow MR sequence (PC-VIPR). Flow rates were assessed in the supraceliac (SCAo) and infrarenal aorta, celiac artery, superior mesenteric artery (SMA), left and right renal arteries, superior mesenteric vein (SMV), splenic vein, and portal vein (PV) in a fasting state (preprandial) and 20 min after a 700-kcal meal (postprandial). Patients were subcategorized into positive diagnosis (CMI+, N = 6) and negative diagnosis (CMI-, N = 13) groups based on imaging and clinical findings. Preprandial, postprandial, and percent change in flow rates were compared between subgroups using a Welch t test. RESULTS: In controls and CMI- patients, SCAo, SMA, SMV, and PV flow increased significantly after meal ingestion. No significant flow increases were observed in CMI+ patients. Percent changes in SMA, SMV, and PV flow were significantly greater in controls compared to CMI+ patients. Additionally, percent changes in flow in the SMV and PV were significantly greater in CMI- patients compared to CMI+ patients. CONCLUSIONS: 4D flow MRI with large volumetric coverage demonstrated significant differences in the redistribution of blood flow in SMA, SMV, and PV in CMI+ patients after a meal challenge. This approach may assist in the challenging diagnosis of CMI.

Abdominal applications of quantitative 4D flow MRI.

4D flow MRI is a quantitative MRI technique that allows the comprehensive assessment of time-resolved hemodynamics and vascular anatomy over a 3-dimensional imaging volume. It effectively combines several advantages of invasive and non-invasive imaging modalities like ultrasound, angiography, and computed tomography in a single MRI acquisition and provides an unprecedented characterization of velocity fields acquired non-invasively in vivo. Functional and morphological imaging of the abdominal vasculature is especially challenging due to its complex and variable anatomy with a wide range of vessel calibers and flow velocities and the need for large volumetric coverage. Despite these challenges, 4D flow MRI is a promising diagnostic and prognostic tool as many pathologies in the abdomen are associated with changes of either hemodynamics or morphology of arteries, veins, or the portal venous system. In this review article, we will discuss technical aspects of the implementation of abdominal 4D flow MRI ranging from patient preparation and acquisition protocol over post-processing and quality control to final data analysis. In recent years, the range of applications for 4D flow in the abdomen has increased profoundly. Therefore, we will review potential clinical applications and address their clinical importance, relevant quantitative and qualitative parameters, and unmet challenges.

Virtual injections using 4D flow MRI with displacement corrections and constrained probabilistic streamlines.

PURPOSE: Streamlines from 4D-flow MRI have been used clinically for intracranial blood-flow tracking. However, deterministic and stochastic errors degrade streamline quality. The purpose of this study is to integrate displacement corrections, probabilistic streamlines, and novel fluid constraints to improve selective blood-flow tracking and emulate "virtual bolus injections." METHODS: Both displacement artifacts (deterministic) and velocity noise (stochastic) inherently occur during phase-contrast MRI acquisitions. Here, two displacement correction methods, single-step and iterative, were tested in silico with simulated displacements and were compared with ground-truth velocity fields. Next, the effects of combining displacement corrections and constrained probabilistic streamlines were performed in 10 healthy volunteers using time-averaged 4D-flow data. Measures of streamline length and depth into vasculature were then compared with streamlines generated with no corrections and displacement correction alone using one-way repeated-measures analysis of variance and Friedman's tests. Finally, virtual injections with improved streamlines were generated for three intracranial pathology cases. RESULTS: Iterative displacement correction outperformed the single-step method in silico. In volunteers, the combination of displacement corrections and constrained probabilistic streamlines allowed for significant improvements in streamline length and increased the number of streamlines entering the circle of Willis relative to streamlines with no corrections and displacement correction alone. In the pathology cases, virtual injections with improved streamlines were qualitatively similar to dynamic arterial spin labeling images and allowed for forward/reverse selective flow tracking to characterize cerebrovascular malformations. CONCLUSION: Virtual injections with improved streamlines from 4D-flow MRI allow for flexible, robust, intracranial flow tracking.

Exercise-induced irregular right heart flow dynamics in adolescents and young adults born preterm.

BACKGROUND: Preterm birth has been linked to an elevated risk of heart failure and cardiopulmonary disease later in life. With improved neonatal care and survival, most infants born preterm are now reaching adulthood. In this study, we used 4D flow cardiovascular magnetic resonance (CMR) coupled with an exercise challenge to assess the impact of preterm birth on right heart flow dynamics in otherwise healthy adolescents and young adults who were born preterm. METHODS: Eleven young adults and 17 adolescents born preterm (< 32 weeks of gestation and < 1500 g birth weight) were compared to 11 young adult and 18 adolescent age-matched controls born at term. Stroke volume, cardiac output, and flow in the main pulmonary artery were quantified with 4D flow CMR. Kinetic energy and vorticity were measured in the right ventricle. All parameters were measured at rest and during exercise at a power corresponding to 70% VO2max for each subject. Multivariate linear regression was used to perform age-adjusted term-preterm comparisons. RESULTS: With exercise, stroke volume increased 10 ± 21% in term controls and decreased 4 ± 18% in preterm born subjects (p = 0.007). This resulted in significantly reduced capacity to increase cardiac output in response to exercise stress for the preterm group (58 ± 26% increase in controls, 36 ± 27% increase in preterm, p = 0.004). Elevated kinetic energy (KEterm = 71 ± 22 nJ, KEpreterm = 87 ± 38 nJ, p = 0.03) and vorticity (ωterm = 79 ± 16 s-1, ωpreterm = 94 ± 32 s-1, p = 0.01) during diastole in the right ventricle (RV) suggested altered RV flow dynamics in the preterm subjects. Streamline visualizations showed altered structure to the diastolic filling vortices in those born preterm. CONCLUSIONS: For the participants examined here, preterm birth appeared to result in altered right-heart flow dynamics as early as adolescence, especially during diastole. Future studies should evaluate whether the altered dynamics identified here evolves into cardiopulmonary disease later in life. Trial registration None.