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In this work, we describe the CRIMSON (CardiovasculaR Integrated Modelling and SimulatiON) software environment. CRIMSON provides a powerful, customizable and user-friendly system for performing three-dimensional and reduced-order computational haemodynamics studies via a pipeline which involves: 1) segmenting vascular structures from medical images; 2) constructing analytic arterial and venous geometric models; 3) performing finite element mesh generation; 4) designing, and 5) applying boundary conditions; 6) running incompressible Navier-Stokes simulations of blood flow with fluid-structure interaction capabilities; and 7) post-processing and visualizing the results, including velocity, pressure and wall shear stress fields. A key aim of CRIMSON is to create a software environment that makes powerful computational haemodynamics tools accessible to a wide audience, including clinicians and students, both within our research laboratories and throughout the community. The overall philosophy is to leverage best-in-class open source standards for medical image processing, parallel flow computation, geometric solid modelling, data assimilation, and mesh generation. It is actively used by researchers in Europe, North and South America, Asia, and Australia. It has been applied to numerous clinical problems; we illustrate applications of CRIMSON to real-world problems using examples ranging from pre-operative surgical planning to medical device design optimization.

Objective: This study investigated the accuracy of two oscillometric devices for measuring brachial and central blood pressures (BP) in children and adolescents, using high fidelity intra-arterial measurements as a gold-standard reference. Methods: 57 children and adolescents aged 9.5 ± 4.6 years (mean ± SD, range 3 to 17, 74% 0.18). Results in sub-groups ≥13 and

Objective: To assess whether reservoir pressure (Pres) in young individuals with a compliant aorta is uniform throughout the aorta, as has recently been reported in older adults with cardiovascular disease (1). Methods: High fidelity pressure was measured with a Verrata wire (Philips Volcano) in 5 aortic locations (ascending-to-abdominal) via pull-back in 11 children with a normal aorta (age 10.4 ± 4.9 years, mean ± SD). Pres was calculated using the ‘pressure-only’ approach (2), with exponential fitting over the whole of diastole (1) (WholeDia) or the period when pressure declined in an approximately exponential fashion (ExpDia). Results: ExpDia produced a better fit than WholeDia (R2=0.99 ± 0.01 vs 0.91 ± 0.11, P < 0.001). Pres amplitude (ΔPres) in the ascending aorta from WholeDia fitting (12.0 ± 4.1 mmHg) was less than with ExpDia fitting (19.0 ± 5.2, P = 0.001). The zero-flow asymptotic pressure (Pinf) obtained from the fitting procedure was negative (non-physiological) in 76% (WholeDia) and 44% (ExpDia) of recordings, but fixing Pinf to 37 mmHg (average of physiological values) had little effect on the resulting ΔPres. ΔPres varied by 5.7 ± 3.0 mmHg (WholeDia) and 7.3 ± 3.7 mmHg (ExpDia) between aortic locations (both P

Background: Wave reflection (caused by a stiffness increase from large to small arteries) has been considered to protect against high microvasculature Pulse Pressures (mPP) (1). However, according to transmission line theory, Transmission (T) and Reflection (R) coefficients are proportional (T = 1+R), implying that reflection would not be protective. Proximal arterial stiffening with aging is associated with reduced Total Arterial Compliance (TAC) and increased forward Pressure (Pfw). We hypothesized that a high TAC and low Pfw, rather than high R, are responsible for protection from mPP. Methods: We constructed a fractal arterial tree containing 5008 vessels across 14 generations (fractal exponent 2.76, asymmetry ratio 0.8). Wave speed in each vessel was prescribed to achieve a uniform reflection coefficient (R = -0.025, 0, 0.025 or 0.05) at every junction, achieved by progressively stiffening distal vessels while keeping aortic wave speed constant (“distal-stiffening”) or by progressively stiffening proximal vessels while keeping average wave speed in all terminal vessels constant (“proximal-stiffening”, see Figure. An elastance heart model was applied at the inlet and simulations were performed with a one-dimensional flow solver (2). Results: Proximal-stiffening and distal-stiffening had opposing effects on R but the same effects on mPP, whereas mPP increased monotonically with decreasing TAC and increasing Pfw in both settings (Figure). Conclusion: Wave reflection per se does not provide protection from high mPP since greater reflection also entails greater transmitted pressure. Although a decreased R may accompany proximal arterial stiffening, the likely mechanism of increased mPP with aging is decreased TAC and greater Pfw.

Background and Aims: The increase in arterial stiffness and pressure pulsatility with age is identified as a key contributor to cognitive impairment; nevertheless, the underlying hemodynamic mechanisms remain unclear. A hypothesis, proposed by (1), suggests that the preferential stiffening of the central arteries as compared to the periphery changes the impedance distribution of the arterial network and exposes the cerebral circulation to the deleterious effects of excessive pulsatile energy. The aim of the present study was to test this hypothesis using a previously developed mathematical model of the ageing cardiovascular system (2). Methods: For each decade of age, forward and backward components of wave and hydraulic power and energy were calculated (3) at the ascending aorta as well as at the cerebral blood supply vessels, i.e. the vertebral and internal carotid arteries. Subsequently, we isolated the component of hydraulic energy (HE) related to the initial forward compression wave (FCW) by restricting the analysis to early systole (0–0.2 sec) and calculated the respective energy transmission coefficients. Results: Ageing was associated with an increase in proximal aortic FCW wave power (dictated by the augmented ventricular contractility) and a slight increase in total hydraulic energy. The FCW energy transmission coefficients were almost doubled for all brain vessels as shown in Fig. 1. Conclusion: Our findings support the hypothesis that age-related central arterial stiffening leads to an enhanced energy transmission of the early systolic forward wave towards brain vessels, potentially contributing to impaired brain function with increasing age.

Objective: The aims of this study in children were to 1) evaluate two brachial oscillometric devices for estimating central augmentation index (AIx) and reflection magnitude (RM), and 2) test whether AIx or RM are associated with left ventricular mass index (LVMI). Methods: Intra-aortic (IA) AIx was calculated from high-fidelity pressure measured with a Verrata wire (Philips Volcano) in 60 children (9.2 ± 4.7 years) with unobstructed aorta undergoing clinically-indicated catheterisation. AIx was also obtained from SphygmoCor XCEL (SC, AtCor) and/or Mobil-o-Graph (MB, IEM) brachial oscillometric devices. RM(IA) was calculated via wave separation using a representative normalised flow waveform obtained from MRI in a separate group of normal adolescents, RM(SC) via the triangulation method, and RM(MB) provided by the proprietary software. LVMI was estimated via echocardiography. Results: Invasive vs non-invasive AIx and RM are compared in the Table. AIx(IA) correlated weakly with AIx(SC) (R = 0.27, P = 0.04) but not AIx(MB) (P = 0.4). Neither RM(SC) nor RM(MB) correlated with RM(IA) (P = 0.13 and P = 0.96 respectively). RM(IA) was moderately correlated with AIx(IA) (R = 0.69, P < 0.001) and weakly correlated with AIx(SC) (R = 0.36, P = 0.007) but not AIx(MB) (P = 0.7). In a multivariable regression, height (P < 0.001) and RM (IA) (P = 0.04) were independently and positively associated with LVMI (adjusted R2 = 0.24), whereas there were no associations of any AIx or non-invasively estimated RM with LVMI. Conclusion: Central AIx and RM were poorly estimated by SC and MB in children. Unlike RM(IA), none of the non-invasive indices of wave reflection correlated with LVMI, likely due to inadequate estimation of the central pressure waveform shape in this age group.

Objective: Reservoir-excess pressure measured using tonometry methods predicts cardiovascular events, but the operator-dependency of tonometry is an impediment to widespread use. A cuff-based blood pressure device has been developed to derive reservoir-excess pressure from measured brachial pressure waveforms, but whether this method is independently associated with cardiovascular risk has never been investigated and this was the aim of this study. Methods: 1874 adult participants (age 43.7 ± 5.2 years, 11% male) from the Longitudinal Study of Australian Children’s Child Health CheckPoint study had reservoir pressure (RP) and excess pressure (XSP) derived from the brachial pressure waveform measured using cuff oscillometry (SphygmoCor XCEL, AtCor Medical, Sydney). Central hemodynamics (augmentation index and central blood pressure) were estimated from the central pressure waveform. Carotid intima-media thickness (cIMT, n = 1467) and carotid-to-femoral pulse wave velocity (cf-PWV, n = 1674) were measured as end-organ markers of cardiovascular risk. Results: XSP and RP were associated with cIMT after adjusting for age, sex, waist-to-hip ratio, heart rate (HR) and central hemodynamic indices (β = 0.070, p = 0.027 and β = 0.052, p = 0.047). RP was also significantly associated with cf-PWV after adjusting for the same variables as above (β = 0.128, p < 0.001). The additional reservoir-excess pressure variables in a model that originally included the Framingham risk score and HR strengthened the evidence for associations with cIMT and cf-PWV (p < 0.001 for all R2 changes). Conclusion: Cuff-based measures of reservoir-excess pressure are significantly associated with end-organ markers of cardiovascular risk independent of traditional risk factors. This cuff method may provide additional information to improve cardiovascular risk stratification.

Introduction: Reservoir pressure (RP) and excess pressure (XSP) independently predict cardiovascular events in adults, but have never been investigated as markers of cardiovascular risk among children. This study aimed to determine the association of RP and XSP with end-organ makers of cardiovascular risk related to kidney function and large artery pre-atherosclerosis. Methods: Participants were 1874 11–12 year-old children (50% male) from the Longitudinal Study of Australian Children’s Child Health CheckPoint study. Brachial blood pressure was measured by cuff oscillometric device (SphygmoCor XCEL, AtCor, Sydney). The same device was used to derive reservoir pressure (RP) and excess pressure (XSP) from the brachial pressure waveform. Kidney function was determined from estimated glomerular filtration rate (eGFR, n = 926) and large artery pre-atherosclerosis was determined from carotid intima media thickness (cIMT, n = 1131) using ultrasound. Results: The eGFR was significantly correlated with RP peak (r = −0.109, p = 0.001), RP integral (r = −0.136, p < 0.001), XSP peak (r = 0.096, p = 0.004) and XSP integral (r = 0.102, p = 0.002). The RP (whether expressed as peak or integral) was significantly associated with eGFR after adjusting for sex, waist-to-hip ratio, heart rate and brachial BP indices (RP peak β = −0.079, p = 0.02, partial R2 = 0.006 and RP integral β = −0.079, p = 0.02, partial R2 = 0.007). XSP was not independently associated with eGFR after adjusting for the above variables. Neither RP nor XSP were significantly associated with cIMT. Conclusion: Independent of conventional risk factors, RP was significantly associated with kidney function among a large population of Australian children. The non-invasive method to derive RP using an oscillometric cuff device could provide useful clinical information in children.