Regional and Global Aortic Pulse Wave Velocity in Patients with Abdominal Aortic Aneurysm.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is commonly defined as localised aortic dilatation with a diameter > 30 mm. The pathophysiology of AAA includes chronic inflammation and enzymatic degradation of elastin, possibly increasing aortic wall stiffness and pulse wave velocity (PWV). Whether aortic stiffness is more prominent in the abdominal aorta at the aneurysm site is not elucidated. The aim of this study was to evaluate global and regional aortic PWV in patients with AAA. METHODS: Experimental study of local PWV in the thoracic descending and abdominal aorta in patients with AAA and matched controls. The study cohort comprised 25 patients with an AAA > 30 mm (range 36 - 70 mm, all male, age range 65 - 76 years) and 27 age and sex matched controls free of AAA. PWV was measured with applanation tonometry (carotid-femoral PWV, cfPWV) as well as a 4D flow MRI technique, assessing regional aortic PWV. Blood pressure and anthropometrics were measured. RESULTS: Global aortic PWV was greater in men with an AAA than controls, both by MRI (AAA 8.9 ± 2.4 m/s vs. controls 7.1 ± 1.5 m/s; p = .007) and cfPWV (AAA 11.0 ± 2.1 m/s vs. controls 9.3 ± 2.3 m/s; p = .007). Regionally, PWV was greater in the abdominal aorta in the AAA group (AAA 7.0 ± 1.8 m/s vs. controls 5.8 ± 1.0 m/s; p = .022), but similar in the thoracic descending aorta (AAA 8.7 ± 3.2 m/s vs. controls 8.2 ± 2.4 m/s; p = .59). Furthermore, PWV was positively associated with indices of central adiposity both in men with AAA and controls. CONCLUSION: PWV is higher in men with AAA compared with matched controls in the abdominal but not the thoracic descending aorta. Furthermore, aortic stiffness was linked with central fat deposition. It remains to be seen whether there is a causal link between AAA and increased regional aortic stiffness.

Helical flow in tortuous aortas and its relationship to turbulence: A whole-aorta 4D flow MRI study.

Background: Increased vascular tortuosity is a hallmark of ageing of the vascular system, including the aorta. However, the impact of tortuosity on aortic blood flow is unknown. We hypothesized that increased tortuosity would be associated with increased blood flow helicity and with decreased degree of blood flow turbulence as measured by the turbulent kinetic energy (TKE). Methods: 4D Flow MR images covering the entire aorta from the aortic valve to the iliac bifurcation were acquired in 23 normal volunteers aged 18-30 years ("Young") and 23 normal volunteers aged 66-76 years ("Old") without aortic disease. The aorta was segmented and divided into four regions: the ascending, descending, suprarenal abdominal and infrarenal abdominal aorta. Tortuosity, helicity, TKE, flow velocity, and Reynolds number were computed for the whole aorta and for each section. Results: Tortuosity and helicity were higher whereas TKE, velocity, and Reynolds number were lower in Old than in Young, for all aortic regions (p < 0.05) except for helicity in the descending aorta. Tortuosity correlated positively with helicity and negatively with TKE for all aortic regions (Spearman rho=±0.45-±0.72, p < =0.002) except for TKE in the ascending aorta. Further, helicity correlated with TKE in the descending, suprarenal abdominal and infrarenal abdominal aorta (Spearman rho=-0.56--0.77). Conclusion: Tortuosity increases with age and blood flow in tortuous aortas is more helical. Increasing helicity, in turn, is associated with decreasing TKE.

Wall shear stress and relative residence time as potential risk factors for abdominal aortic aneurysms in males: a 4D flow cardiovascular magnetic resonance case-control study.

BACKGROUND: Abdominal aortic aneurysms (AAA) can lead to catastrophic events such as dissection or rupture, and are an expression of general aortic disease. Low wall shear stress (WSS), high oscillatory shear index (OSI), and high relative residence time (RRT) have been correlated against increased uptake of inflammatory markers in the vessel wall and may improve risk stratification of AAA. We sought to obtain a comprehensive view of WSS, OSI, and RRT in the whole aorta for patients with AAA and age-matched elderly controls and young normal controls. METHODS: 4D Flow cardiovascular magnetic resonance images of the whole aorta were acquired in 18 AAA patients (70.8 ± 3.4 years), 22 age-matched controls (71.4 ± 3.4 years), and 23 young subjects (23.3 ± 3.1 years), all males. Three-dimensional segmentations of the whole aorta were created for all timeframes using a semi-automatic approach. The aorta was divided into five segments: ascending aorta, arch, descending aorta, suprarenal and infrarenal abdominal aorta. For each segment, average values of peak WSS, OSI, and RRT were computed. Student's t-tests were used to compare values between the three cohorts (AAA patients vs elderly controls, and elderly controls vs young controls) where the data were normally distributed, and the non-parametric Wilcoxon rank sum tests were used otherwise. RESULTS: AAA patients had lower peak WSS in the descending aorta as well as in the abdominal aorta compared to elderly controls (p ≤ 0.001), similar OSI, but higher RRT in the descending and abdominal aorta (p ≤ 0.001). Elderly controls had lower peak WSS compared to young controls throughout the aorta (p < 0.001), higher OSI in all segments except for the infrarenal aorta (p < 0.001), and higher RRT throughout the aorta, except the infrarenal aorta (p < 0.001). CONCLUSIONS: This study provides novel insights into WSS, OSI, and RRT in patients with AAA in relation to normal ageing, highlighting how AAA patients have markedly abnormal hemodynamic stresses not only in the infrarenal, but in the entire aorta. Moreover, we identified RRT as a marker for abnormal AAA hemodynamics. Further investigations are needed to explore if RRT or other measures of hemodynamics stresses best predict AAA growth and/or rupture.

Quantitative Magnetic Resonance Imaging Assessment of the Relationships Between Fat Fraction and R2* Inside Carotid Plaques, and Circulating Lipoproteins.

BACKGROUND: Lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) are morphological features of high-risk atherosclerotic plaques. However, their relationship to circulating lipoproteins is unclear. PURPOSE: To study associations between changes in lipoproteins vs. changes in LRNC (represented by fat fraction [FF]) and IPH (represented by R2*). STUDY TYPE: Prospective. SUBJECTS: Fifty-two patients with carotid plaques, 33 males (63.5%), mean age 72 (±5). FIELD STRENGTH/SEQUENCE: Four-point fast gradient Dixon magnetic resonance imaging (MRI) was used to quantify FF and R2* (to measure IPH) inside plaques and in vessel wall. Turbo-spin echo was used for T1 weighted sequences to guide manual segmentation. ASSESSMENT: Carotid MRI and serum lipid levels were assessed at baseline and at 1-year follow-up. For patients, lipid-lowering therapy was customized to reduce low-density lipoprotein (LDL) levels below 1.8 mmol/L. Segmentation was performed with one set of regions of interest for the plaque and one for the vessel wall at the location of the plaque. Thereby MRI data for FF, R2*, and volumes in plaque- and vessel-wall segmentations could be obtained from baseline and follow-up, as well as changes over the study year. STATISTICAL TESTS: Pearson correlation coefficient for correlations. Paired samples t-test for changes over time. Significance at P < 0.05, 95% confidence interval. RESULTS: LDL decreased significantly (2.19-1.88 mmol/L, Z - 2.9), without correlation to changes in plaque composition, nor to the significant reduction in vessel-wall volume (-106.3 mm3 ). Plaque composition remained unchanged, FF +8.5% (P = 0.366) and R2* +3.5% (P = 0.304). Compared to plaque segmentations, R2* was significantly lower in the vessel-wall segmentations both at baseline (-9.3%) and at follow-up (-9.1%). DATA CONCLUSION: The absence of correlations between changes in lipoproteins and changes in plaque composition indicates more complex relationships between these parameters than previously anticipated. The significant differences in both R2* and volume dynamics comparing plaque segmentations and vessel-wall segmentations suggest differences in their pathobiology of atherosclerosis. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

18Fluorodeoxyglucose uptake in relation to fat fraction and R2* in atherosclerotic plaques, using PET/MRI: a pilot study.

Inflammation inside Atherosclerotic plaques represents a major pathophysiological process driving plaques towards rupture. Pre-clinical studies suggest a relationship between lipid rich necrotic core, intraplaque hemorrhage and inflammation, not previously explored in patients. Therefore, we designed a pilot study to investigate the feasibility of assessing the relationship between these plaque features in a quantitative manner using PET/MRI. In 12 patients with high-grade carotid stenosis the extent of lipid rich necrotic core and intraplaque hemorrhage was quantified from fat and R2* maps acquired with a previously validated 4-point Dixon MRI sequence in a stand-alone MRI. PET/MRI was used to measure 18F-FDG uptake. T1-weighted images from both scanners were used for registration of the quantitative Dixon data with the PET images. The plaques were heterogenous with respect to their volumes and composition. The mean values for the group were as follows: fat fraction (FF) 0.17% (± 0.07), R2* 47.6 s-1 (± 10.9) and target-to-blood pool ratio (TBR) 1.49 (± 0.48). At group level the correlation between TBR and FFmean was - 0.406, p 0.19 and for TBR and R2*mean 0.259, p 0.42. The lack of correlation persisted when analysed on a patient-by-patient basis but the study was not powered to draw definitive conclusions. We show the feasibility of analysing the quantitative relationship between lipid rich necrotic cores, intraplaque haemorrhage and plaque inflammation. The 18F-FDG uptake for most patients was low. This may reflect the biological complexity of the plaques and technical aspects inherent to 18F-FDG measurements.Trial registration: ISRCTN, ISRCTN30673005. Registered 05 January 2021, retrospectively registered.

Automated segmentation of the individual branches of the carotid arteries in contrast-enhanced MR angiography using DeepMedic.

BACKGROUND: Non-invasive imaging is of interest for tracking the progression of atherosclerosis in the carotid bifurcation, and segmenting this region into its constituent branch arteries is necessary for analyses. The purpose of this study was to validate and demonstrate a method for segmenting the carotid bifurcation into the common, internal, and external carotid arteries (CCA, ICA, ECA) in contrast-enhanced MR angiography (CE-MRA) data. METHODS: A segmentation pipeline utilizing a convolutional neural network (DeepMedic) was tailored and trained for multi-class segmentation of the carotid arteries in CE-MRA data from the Swedish CardioPulmonsary bioImage Study (SCAPIS). Segmentation quality was quantitatively assessed using the Dice similarity coefficient (DSC), Matthews Correlation Coefficient (MCC), F2, F0.5, and True Positive Ratio (TPR). Segmentations were also assessed qualitatively, by three observers using visual inspection. Finally, geometric descriptions of the carotid bifurcations were generated for each subject to demonstrate the utility of the proposed segmentation method. RESULTS: Branch-level segmentations scored DSC = 0.80 ± 0.13, MCC = 0.80 ± 0.12, F2 = 0.82 ± 0.14, F0.5 = 0.78 ± 0.13, and TPR = 0.84 ± 0.16, on average in a testing cohort of 46 carotid bifurcations. Qualitatively, 61% of segmentations were judged to be usable for analyses without adjustments in a cohort of 336 carotid bifurcations without ground-truth. Carotid artery geometry showed wide variation within the whole cohort, with CCA diameter 8.6 ± 1.1 mm, ICA 7.5 ± 1.4 mm, ECA 5.7 ± 1.0 mm and bifurcation angle 41 ± 21°. CONCLUSION: The proposed segmentation method automatically generates branch-level segmentations of the carotid arteries that are suitable for use in further analyses and help enable large-cohort investigations.

Towards Automated Quantification of Vessel Wall Composition Using MRI.

BACKGROUND: MRI can be used to generate fat fraction (FF) and R2* data, which have been previously shown to characterize the plaque compositional features lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in the carotid arteries (CAs). Previously, these data were extracted from CA plaques using time-consuming manual analyses. PURPOSE: To design and demonstrate a method for segmenting the CA and extracting data describing the composition of the vessel wall. STUDY TYPE: Prospective. SUBJECTS: 31 subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS). FIELD STRENGTH/SEQUENCES: T1 -weighted (T1 W) quadruple inversion recovery, contrast-enhanced MR angiography (CE-MRA), and 4-point Dixon data were acquired at 3T. ASSESSMENT: The vessel lumen of the CA was automatically segmented using support vector machines (SVM) with CE-MRA data, and the vessel wall region was subsequently delineated. Automatically generated segmentations were quantitatively measured and three observers visually compared the segmentations to manual segmentations performed on T1 w images. Dixon data were used to generate FF and R2* maps. Both manually and automatically generated segmentations of the CA and vessel wall were used to extract compositional data. STATISTICAL TESTS: Two-tailed t-tests were used to examine differences between results generated using manual and automated analyses, and among different configurations of the automated method. Interobserver agreement was assessed with Fleiss' kappa. RESULTS: Automated segmentation of the CA using SVM had a Dice score of 0.89 ± 0.02 and true-positive ratio 0.93 ± 0.03 when compared against ground truth, and median qualitative score of 4/5 when assessed visually by multiple observers. Vessel wall regions of 0.5 and 1 mm yielded compositional information similar to that gained from manual analyses. Using the 0.5 mm vessel wall region, the mean difference was 0.1 ± 2.5% considering FF and 1.1 ± 5.7[1/s] for R2*. LEVEL OF EVIDENCE: 1. TECHNICAL EFFICACY STAGE: 1. J. Magn. Reson. Imaging 2020;52:710-719.

Exploring the Relationships Between Hemodynamic Stresses in the Carotid Arteries.

Background: Atherosclerosis manifests as a focal disease, often affecting areas with complex hemodynamics such as the carotid bifurcation. The magnitude and regularity of the hemodynamic shear stresses acting on the vessel wall are thought to generate risk patterns unique to each patient and play a role in the pathogenesis of atherosclerosis. The involvement of different expressions of shear stress in the pathogenesis of carotid atherosclerosis highlights the need to characterize and compare the differential impact of the various expressions of shear stress in the atherosclerotic carotid bifurcation. Therefore, the aim of this study is to characterize and compare hemodynamic wall shear stresses (WSS) in the carotid arteries of subjects with asymptomatic atherosclerotic plaques. Shear stresses were also compared against vessel diameter and bifurcation angle to examine the relationships with the geometry of the carotid bifurcation. Methods: 4D Flow MRI and contrast-enhanced MRA data were acquired for 245 subjects with atherosclerotic plaques of at least 2.7 mm in conjunction with the Swedish CArdioPulmonary bioImage Study (SCAPIS). Following automatic segmentation and geometric analysis, time-resolved WSS and near-wall turbulent kinetic energy (nwTKE) were derived from the 4D Flow data. Whole-cycle parameters including time-averaged WSS and nwTKE, and the oscillatory shear index (OSI) were calculated. Pairwise Spearman rank-correlation analyses were used to investigate relationships among the hemodynamic as well as geometric parameters. Results: One hundred and seventy nine subjects were successfully segmented using automated tools and subsequently geometric and hemodynamic analyses were performed. Temporally resolved WSS and nwTKE were strongly correlated, ρ = 0.64. Cycle-averaged WSS and nwTKE were moderately correlated, ρ = 0.57. Cycle-average nwTKE was weakly correlated to OSI (ρ = -0.273), revealing that nwTKE provides information about disturbed flow on the vessel wall that OSI does not. In this cohort, there was large inter-individual variation for both WSS and nwTKE. Both WSS and nwTKE varied most within the external carotid artery. WSS, nwTKE, and OSI were weakly correlated to vessel diameter and bifurcation angle. Conclusion: The turbulent and mean component of WSS were examined together in vivo for the first time, and a strong correlation was found between them. nwTKE presents the opportunity to quantify turbulent wall stresses in vivo and gain insight into the effects of disturbed flow on the vessel wall. Neither vessel diameter nor bifurcation angle were found to be strongly correlated to the turbulent or mean component of WSS in this cohort.

Visualizing and quantifying flow stasis in abdominal aortic aneurysms in men using 4D flow MRI.

PURPOSE: To examine methods for visualizing and quantifying flow stasis in abdominal aortic aneurysms (AAA) using 4D Flow MRI. METHODS: Three methods were investigated: conventional volumetric residence time (VRT), mean velocity analysis (MVA), and particle travel distance analysis (TDA). First, ideal 4D Flow MRI data was generated using numerical simulations and used as a platform to explore the effects of noise and background phase-offset errors, both of which are common 4D Flow MRI artifacts. Error-free results were compared to noise or offset affected results using linear regression. Subsequently, 4D Flow MRI data for thirteen (13) subjects with AAA was acquired and used to compare the stasis quantification methods against conventional flow visualization. RESULTS: VRT (R2 = 0.69) was more sensitive to noise than MVA (R2 = 0.98) and TDA (R2 = 0.99) at typical non-contrast signal-to-noise ratio levels (SNR = 20). VRT (R2 = 0.14) was more sensitive to background phase-offsets than MVA (R2 = 0.99) and TDA (R2 = 0.96) when considering a 95% effective background phase-offset correction. Qualitatively, TDA outperformed MVA (Wilcoxon p < 0.005, mean score improvement 1.6/5), and had good agreement (median score 4/5) with flow visualizations. CONCLUSION: Flow stasis can be quantitatively assessed using 4D Flow MRI. While conventional residence time calculations fail due to error accumulation as a result of imperfect measured velocity fields, methods that do not require lengthy particle tracking perform better. MVA and TDA are less sensitive to measurement errors, and TDA generates results most similar to those obtained using conventional flow visualization.

Age-Related Vascular Changes Affect Turbulence in Aortic Blood Flow.

Turbulent blood flow is implicated in the pathogenesis of several aortic diseases but the extent and degree of turbulent blood flow in the normal aorta is unknown. We aimed to quantify the extent and degree of turbulece in the normal aorta and to assess whether age impacts the degree of turbulence. 22 young normal males (23.7 ± 3.0 y.o.) and 20 old normal males (70.9 ± 3.5 y.o.) were examined using four dimensional flow magnetic resonance imaging (4D Flow MRI) to quantify the turbulent kinetic energy (TKE), a measure of the intensity of turbulence, in the aorta. All healthy subjects developed turbulent flow in the aorta, with total TKE of 3-19 mJ. The overall degree of turbulence in the entire aorta was similar between the groups, although the old subjects had about 73% more total TKE in the ascending aorta compared to the young subjects (young = 3.7 ± 1.8 mJ, old = 6.4 ± 2.4 mJ, p < 0.001). This increase in ascending aorta TKE in old subjects was associated with age-related dilation of the ascending aorta which increases the volume available for turbulence development. Conversely, age-related dilation of the descending and abdominal aorta decreased the average flow velocity and suppressed the development of turbulence. In conclusion, turbulent blood flow develops in the aorta of normal subjects and is impacted by age-related geometric changes. Non-invasive assessment enables the determination of normal levels of turbulent flow in the aorta which is a prerequisite for understanding the role of turbulence in the pathophysiology of cardiovascular disease.

Estimating the irreversible pressure drop across a stenosis by quantifying turbulence production using 4D Flow MRI.

The pressure drop across a stenotic vessel is an important parameter in medicine, providing a commonly used and intuitive metric for evaluating the severity of the stenosis. However, non-invasive estimation of the pressure drop under pathological conditions has remained difficult. This study demonstrates a novel method to quantify the irreversible pressure drop across a stenosis using 4D Flow MRI by calculating the total turbulence production of the flow. Simulation MRI acquisitions showed that the energy lost to turbulence production can be accurately quantified with 4D Flow MRI within a range of practical spatial resolutions (1-3 mm; regression slope = 0.91, R2 = 0.96). The quantification of the turbulence production was not substantially influenced by the signal-to-noise ratio (SNR), resulting in less than 2% mean bias at SNR > 10. Pressure drop estimation based on turbulence production robustly predicted the irreversible pressure drop, regardless of the stenosis severity and post-stenosis dilatation (regression slope = 0.956, R2 = 0.96). In vitro validation of the technique in a 75% stenosis channel confirmed that pressure drop prediction based on the turbulence production agreed with the measured pressure drop (regression slope = 1.15, R2 = 0.999, Bland-Altman agreement = 0.75 ± 3.93 mmHg).

Assessment of turbulent flow effects on the vessel wall using four-dimensional flow MRI.

PURPOSE: To explore the use of MR-estimated turbulence quantities for the assessment of turbulent flow effects on the vessel wall. METHODS: Numerical velocity data for two patient-derived models was obtained using computational fluid dynamics (CFD) for two physiological flow rates. The four-dimensional (4D) Flow MRI measurements were simulated at three different spatial resolutions and used to investigate the estimation of turbulent wall shear stress (tWSS) using the intravoxel standard deviation (IVSD) of velocity and turbulent kinetic energy (TKE) estimated near the vessel wall. RESULTS: Accurate estimation of tWSS using the IVSD is limited by the spatial resolution achievable with 4D Flow MRI. TKE, estimated near the wall, has a strong linear relationship to the tWSS (mean R2 = 0.84). Near-wall TKE estimates from MR simulations have good agreement to CFD-derived ground truth (mean R2 = 0.90). Maps of near-wall TKE have strong visual correspondence to tWSS. CONCLUSION: Near-wall estimation of TKE permits assessment of relative maps of tWSS, but direct estimation of tWSS is challenging due to limitations in spatial resolution. Assessment of tWSS and near-wall TKE may open new avenues for analysis of different pathologies. Magn Reson Med 77:2310-2319, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Assessment of turbulent viscous stress using ICOSA 4D Flow MRI for prediction of hemodynamic blood damage.

Flow-induced blood damage plays an important role in determining the hemodynamic impact of abnormal blood flow, but quantifying of these effects, which are dominated by shear stresses in highly fluctuating turbulent flow, has not been feasible. This study evaluated the novel application of turbulence tensor measurements using simulated 4D Flow MRI data with six-directional velocity encoding for assessing hemodynamic stresses and corresponding blood damage index (BDI) in stenotic turbulent blood flow. The results showed that 4D Flow MRI underestimates the maximum principal shear stress of laminar viscous stress (PLVS), and overestimates the maximum principal shear stress of Reynolds stress (PRSS) with increasing voxel size. PLVS and PRSS were also overestimated by about 1.2 and 4.6 times at medium signal to noise ratio (SNR) = 20. In contrast, the square sum of the turbulent viscous shear stress (TVSS), which is used for blood damage index (BDI) estimation, was not severely affected by SNR and voxel size. The square sum of TVSS and the BDI at SNR >20 were underestimated by less than 1% and 10%, respectively. In conclusion, this study demonstrated the feasibility of 4D Flow MRI based quantification of TVSS and BDI which are closely linked to blood damage.