Computational investigation in the aorta of children with Turner syndrome

The aortic arch has complex flow dynamics, with locations of arterial curvature and bifurcation known to be prone to endothelial dysfunction one of the early biological markers for atherosclerotic lesions that underlie most cardiovascular disease. This is particularly relevant to conditions of obesity, which is believed to accelerate the initiation and progression of vascular changes. A computational investigation found morphological differences between the patient-specific geometries to have a strong effect on the haemodynamic environment, and low wall shear stress at areas where atherosclerotic lesions have been suggested to develop preferentially

Computational haemodynamics in Turner syndrome patient-specific aortae with PC-MRI obtained boundary conditions

Women with Turner syndrome (TS), a chromosomal condition in which a female has complete or partial absence of the second sex chromosome, present a unique group of patients, with an increased risk of cardiovascular disease. Mortality rates are three times higher in TS women compared with the general population, and life expectancy is reduced by up to 13 years –the most common cause of death being from cardiovascular disease. Congenital heart abnormalities occur in up to 50% of TS individuals, with bicuspid aortic valve, coarctation of the aorta, and thoracic aortic aneurysm being the most prevalent. Women with TS also have a greater underlying predisposition to metabolic abnormalities, such as obesity, which can exacerbate coronary artery disease, myocardial infarction, and stroke in TS adults. In this study, computational fluid dynamic (CFD)methods were used to analyse the arterial blood flow in children with Turner syndrome, who are known to present an increased risk of obesity and cardiovascular disease. Three-dimensional patient geometries were matched with patient-specific boundary conditions in the first unsteady simulation of blood flow in TS children. Morphological aortic differences between patients were found to have a strong effect on the haemodynamic environment and may be a marker for increased cardiovascular risk

Hemodynamic abnormalities in the aorta of Turner syndrome girls

Congenital abnormalities in girls and women with Turner syndrome (TS), alongside an underlying predisposition to obesity and hypertension, contribute to an increased risk of cardiovascular disease and ultimately reduced life expectancy. We observe that children with TS present a greater variance in aortic arch morphology than their healthy counterparts, and hypothesise that their hemodynamics is also different. In this study, computational fluid dynamic (CFD) simulations were performed for four TS girls, and three age-matched healthy girls, using patient-specific inlet boundary conditions, obtained from phase-contrast MRI data. The visualisation of multidirectional blood flow revealed an increase in vortical flow in the arch, supra-aortic vessels, and descending aorta, and a correlation between the presence of aortic abnormalities and disturbed flow. Compared to the relatively homogeneous pattern of time-averaged wall shear stress (TAWSS) on the healthy aortae, a highly heterogeneous distribution with elevated TAWSS values was observed in the TS geometries. Visualisation of further shear stress parameters, such as oscillatory shear index (OSI), relative residence time (RRT), and transverse WSS (transWSS), revealed dissimilar heterogeneity in the oscillatory and multidirectional nature of the aortic flow. Taking into account the young age of our TS cohort (average age 13 ± 2 years) and their obesity level (75% were obese or overweight), which is believed to accelerate the initiation and progression of endothelial dysfunction, these findings may be an indication of atherosclerotic disease manifesting earlier in life in TS patients. Age, obesity and aortic morphology may, therefore, play a key role in assessing cardiovascular risk in TS children

A pilot study investigating the use of 4D flow MRI for the assessment of splanchnic flow in patients suspected of mesenteric ischaemia

The most common cause of chronic mesenteric ischaemia is atherosclerosis which results in limitation of blood flow to the gastrointestinal tract. This pilot study aimed to evaluate 4D flow MRI as a potential tool for the analysis of blood flow changes post-prandial within the mesenteric vessels. The mesenteric vessels of twelve people were scanned; patients and healthy volunteers. A baseline MRI scan was performed after 6 h of fasting followed by a post-meal scan. Two 4D flow datasets were acquired, over the superior mesenteric artery (SMA) and the main portal venous vessels. Standard 2D time-resolved PC-MRI slices were also obtained across the aorta above the coeliac trunk, superior mesenteric vein, splenic vein and portal vein (PV). In the volunteer cohort there was a marked increase in blood flow post-meal within the PV (p = 0.028), not seen in the patient cohort (p = 0.116). Similarly, there were significant flow changes within the SMA of volunteers (p = 0.028) but not for the patient group (p = 0.116). Our pilot data has shown that there is a significant haemodynamic response to meal challenge in the PV and SMA in normal subjects compared to clinically apparent CMI patients. Therefore, the interrogation of mesenteric venous vessels exclusively is a feasible method to measure post-prandial flow changes in CMI patients

Reconstruction and validation of arterial geometries for computational fluid dynamics using multiple temporal frames of 4D flow-MRI magnitude Images

Purpose Segmentation and reconstruction of arterial blood vessels is a fundamental step in the translation of computational fluid dynamics (CFD) to the clinical practice. Four-dimensional flow magnetic resonance imaging (4D Flow-MRI) can provide detailed information of blood flow but processing this information to elucidate the underlying anatomical structures is challenging. In this study, we present a novel approach to create high-contrast anatomical images from retrospective 4D Flow-MRI data. Methods For healthy and clinical cases, the 3D instantaneous velocities at multiple cardiac time steps were superimposed directly onto the 4D Flow-MRI magnitude images and combined into a single composite frame. This new Composite Phase-Contrast Magnetic Resonance Angiogram (CPC-MRA) resulted in enhanced and uniform contrast within the lumen. These images were subsequently segmented and reconstructed to generate 3D arterial models for CFD. Using the time-dependent, 3D incompressible Reynolds-averaged Navier–Stokes equations, the transient aortic haemodynamics was computed within a rigid wall model of patient geometries. Results Validation of these models against the gold standard CT-based approach showed no statistically significant inter-modality difference regarding vessel radius or curvature (p > 0.05), and a similar Dice Similarity Coefficient and Hausdorff Distance. CFD-derived near-wall hemodynamics indicated a significant inter-modality difference (p > 0.05), though these absolute errors were small. When compared to the in vivo data, CFD-derived velocities were qualitatively similar. Conclusion This proof-of-concept study demonstrated that functional 4D Flow-MRI information can be utilized to retrospectively generate anatomical information for CFD models in the absence of standard imaging datasets and intravenous contrast

Patient-specific computational haemodynamics associated with the surgical creation of an arteriovenous fistula

Despite arteriovenous fistulae (AVF) being the preferred vascular access for haemodialysis, high primary failure rates (30-70%) and low one-year patency rates (40-70%) hamper their use. Furthermore, AVF creation has been associated with haemodynamic changes causing maladaptive cardiac remodelling leading to cardiovascular (CV) complications. In this study, we present a new workflow for characterising the haemodynamic profile prior to and following surgical creation of a successful left radiocephalic AVF in a 20-year-old end-stage kidney disease patient. The reconstructed vasculature was generated using multiple ferumoxytol-enhanced magnetic resonance angiography (FeMRA) datasets. Computational fluid dynamics (CFD) simulations utilising a scale-resolving turbulence model were completed to investigate the changes in the proximal haemodynamics following AVF creation, in addition to the post-AVF juxta-anastomosis flow patterns, which is impractical to obtain in-vivo. Following AVF creation, a significant 2-3-fold increase in blood flow rate was induced downstream of the left subclavian artery. This was validated through comparison with post-AVF patient-specific phase-contrast data. Proximal to the anastomosis, the increased flow rate yielded an increase in time-averaged wall shear stress (WSS), which is a key marker of adaptive vascular remodelling. In the juxta-anastomosis region, the success of the AVF was discussed with respect to the National Kidney Foundation's vascular access guidelines, where the patient-specific AVF met the flow rate and geometry criterion. The AVF venous diameter exceeded 6mm and the venous flow rate surpassed 600mL/min. This workflow may potentially be significant clinically when applied to multi-patient cohorts, with population-wide patient-specific conclusions being ascertained for the haemodynamic assessment of AVFs and improved surgical planning

Image‐based computational fluid dynamics for estimating pressure drop and fractional flow reserve across iliac artery stenosis: a comparison with in‐vivo measurements

Computational Fluid Dynamics (CFD) and time‐resolved phase‐contrast magnetic resonance imaging (PC‐MRI) are potential non‐invasive methods for the assessment of the severity of arterial stenoses. Fractional flow reserve (FFR) is the current “gold standard” for determining stenosis severity in the coronary arteries but is an invasive method requiring insertion of a pressure wire. CFD derived FFR (vFFR) is an alternative to traditional catheter derived FFR now available commercially for coronary artery assessment, however, it can potentially be applied to a wider range of vulnerable vessels such as the iliac arteries. In this study CFD simulations are used to assess the ability of vFFR in predicting the stenosis severity in a patient with a stenosis of 77% area reduction (>50% diameter reduction) in the right iliac artery. Variations of vFFR, overall pressure drop and flow split between the vessels were observed by using different boundary conditions. Correlations between boundary condition parameters and resulting flow variables are presented. The study concludes that vFFR has good potential to characterise iliac artery stenotic disease

Ferumoxytol MR angiography vs Duplex ultrasound for vascular mapping before arteriovenous fistula surgery for hemodialysis

Ferumoxytol-enhanced68 MR angiography was superior to duplex US in the detection of central vein stenosis and arterial disease that correlated with outcomes of arteriovenous fistula surgery for hemodialysis. Background: Duplex US is performed routinely for vascular mapping prior to arteriovenous fistula (AVF) creation for hemodialysis but cannot demonstrate the central vasculature. Ferumoxytol, an iron oxide nanoparticle, provides an alternative to gadolinium contrast material for MR angiography for safe use in chronic kidney disease (CKD). Purpose: To assess the clinical utility of ferumoxytol-enhanced MR angiography compared with duplex US for vascular mapping before upper limb AVF creation in participants with CKD. Materials and Methods: In a prospective comparative study (ClinicalTrials.gov: NCT02997046) from December 2016 to August 2018, participants with CKD underwent ferumoxytol-enhanced MR angiography and duplex US. Two independent readers evaluated vessels for diameter, stenosis or occlusion, arterial disease, and central stenosis. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to assess intra- and interreader variability. On the basis of accepted standards for AVF creation, an algorithm was developed to predict AVF outcome based on imaging findings. Multivariable regression models used AVF success as the dependent variable and age, sex, and duplex US or ferumoxytol-enhanced MR angiography findings as independent variables. Results: Fifty-nine participants with CKD (mean age, 59 years ± 13 [standard deviation]; 30 women) were evaluated. A total of 51 fistulas were created, of which 24 (47%) were successful. Ferumoxytol-enhanced MR angiography showed excellent inter- and intrareader repeatability (ICC, 0.84–0.99) for all variables assessed. In addition to revealing 15 central vasculature stenoses, ferumoxytol-enhanced MR angiography resulted in characterization of 88 of 236 (37%) of the arterial sections examined as unsuitable for AVF creation compared with 61 of 236 (26%) sections with duplex US (P = .01). Ferumoxytol-enhanced MR angiography independently predicted AVF success in models including (odds ratio, 6.5; 95% confidence interval: 1.7, 25; P = .006) and those excluding (odds ratio, 4.6; 95% confidence interval: 1.3, 17; P = .02) the central vasculature. Conclusion: In addition to enabling identification of central vessel pathologic features, ferumoxytol-enhanced MR angiography revealed peripheral arterial disease not recognized with duplex US and was more predictive than duplex US of the outcome of arteriovenous fistula surgery

Psoriatic arthritis is associated with adverse body composition predictive of greater coronary heart disease and type 2 diabetes propensity – a cross-sectional study

Objectives: To compare body composition in PsA with metabolic disease free (MDF) controls and type 2 diabetes and assess body-composition predicted propensity for cardiometabolic disease. Methods: Detailed MRI body composition profiles of 26 PsA participants from the IMAPA study were compared with 130 age, sex and BMI-matched MDF controls and 454 individuals with type 2 diabetes from UK Biobank. The body-composition predicted propensity for coronary heart disease (CHD) and type 2 diabetes was compared between PsA and matched MDF controls. Results: PsA participants had a significantly greater visceral adipose tissue (VAT) volume [mean 5.89 l (S.D. 2.10 l)] compared with matched-MDF controls [mean 4.34 l (S.D. 1.83 l)] (P <0.001) and liver fat percentage [median 8.88% (interquartile range 4.42–13.18%)] compared with MDF controls [3.29% (1.98–7.25%)] (P <0.001). These differences remained significant after adjustment for age, sex and BMI. There were no statistically significant differences in VAT, liver fat or muscle fat infiltration (MFI) between PsA and type 2 diabetes. PsA participants had a lower thigh muscle volume than MDF controls and those with type 2 diabetes. Body composition-predicted propensity for CHD and type 2 diabetes was 1.27 and 1.83 times higher, respectively, for PsA compared with matched-MDF controls. Conclusion: Individuals with PsA have an adverse body composition phenotype with greater visceral and ectopic liver fat and lower thigh muscle volume than matched MDF controls. Body fat distribution in PsA is more in keeping with the pattern observed in type 2 diabetes and is associated with greater propensity to cardiometabolic disease. These data support the need for greater emphasis on weight loss in PsA management to lessen CHD and type 2 diabetes risk

Interrogating the haemodynamic effects of haemodialysis arteriovenous fistula on cardiac structure and function

Arteriovenous fistula (AVF) is the preferred type of vascular access for maintenance haemodialysis but it may contribute to maladaptive cardiovascular remodelling. We studied the effect of AVF creation on cardiac structure and function in patients with chronic kidney disease (CKD). In this prospective cohort study patients with CKD listed for first AVF creation underwent cardiac magnetic resonance (CMR) imaging at baseline and at 6 weeks. All participants had ultrasound measurements of fistula blood flow at 6 weeks. The primary outcome was the change in left ventricular (LV) mass. Secondary outcomes included changes in LV volumes, LV ejection fraction, cardiac output, LV global longitudinal strain and N-terminal-pro B-type natriuretic peptide (NT-proBNP). A total of 55 participants were enrolled, of whom 40 (mean age 59 years) had AVF creation and completed both scans. On the second CMR scan, a mean increase of 7.4 g (95% CI 1.1–13.7, p = 0.02) was observed in LV mass. Significant increases in LV end-diastolic volumes (p = 0.04) and cardiac output (p = 0.02) were also seen after AVF creation. No significant changes were observed in LV end-systolic volumes, LV ejection fraction, NT-proBNP and LV global longitudinal strain. In participants with fistula blood flows ≥ 600 mL/min (n = 22) the mean increase in LV mass was 15.5 g (95% CI 7.3–23.8) compared with a small decrease of 2.5 g (95% CI − 10.6 to 5.6) in participants with blood flows < 600 mL/min (n = 18). Creation of AVF for haemodialysis resulted in a significant increase of LV myocardial mass within weeks after surgery, which was proportional to the fistula flow