CRIMSON: An open-source software framework for cardiovascular integrated modelling and simulation.

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.

Patient-specific modeling of right coronary circulation vulnerability post-liver transplant in Alagille's syndrome.

OBJECTIVES: Cardiac output (CO) response to dobutamine can identify Alagille's syndrome (ALGS) patients at higher risk of cardiovascular complications during liver transplantation. We propose a novel patient-specific computational methodology to estimate the coronary autoregulatory responses during different hemodynamic conditions, including those experienced in a post-reperfusion syndrome (PRS), to aid cardiac risk-assessment. MATERIAL AND METHODS: Data (pressure, flow, strain and ventricular volumes) from a 6-year-old ALGS patient undergoing catheter/dobutamine stress MRI (DSMRI) were used to parameterize a closed-loop coupled-multidomain (3D-0D) approach consisting of image-derived vascular models of pulmonary and systemic circulations and a series of 0D-lumped parameter networks (LPN) of the heart chambers and the distal arterial and venous circulations. A coronary microcirculation control model (CMCM) was designed to adjust the coronary resistance to match coronary blood flow (and thus oxygen delivery) with MVO2 requirements during Rest, Stress and a virtual PRS condition. RESULTS: In all three simulated conditions, diastolic dominated right coronary artery (RCA) flow was observed, due to high right ventricle (RV) afterload. Despite a measured 45% increase in CO, impaired coronary flow reserve (CFR) (~1.4) at Stress was estimated by the CMCM. During modeled PRS, a marked vasodilatory response was insufficient to match RV myocardial oxygen requirements. Such exhaustion of the RCA autoregulatory response was not anticipated by the DSMRI study. CONCLUSION: Impaired CFR undetected by DSMRI resulted in predicted myocardial ischemia in a computational model of PRS. This computational framework may identify ALGS patients at higher risk of complications during liver transplantation due to impaired coronary microvascular responses.

The importance of qualitative and quantitative regional wall motion abnormality assessment at rest in pediatric coronary allograft vasculopathy.

CAV remains one of the main limiting factors for survival in children after heart transplantation. In this study, we explored the incremental value of routine CMR for evaluation and detection of CAV using qualitative and quantitative analysis of regional and global myocardial function and strain. This was a prospective imaging biomarker validation trial. Twenty-two patients (11 male), aged between 10 and 17 years (median 14 years) post-heart transplantation, were prospectively enrolled and underwent CMR in addition to their biennial review workup with Echo, angiography, and IVUS. Nine healthy control patients were enrolled to undergo CMR alone. Echo was used to analyze WMAs and systolic function. CMR images were analyzed qualitatively for RWMA and quantitatively for volumetric analysis, S and SR. All results were compared to IVUS and angiography assessments. Qualitatively, CMR detected RWMA corresponding to angiographic disease in 3 patients that were not detected on Echo. However, quantitative strain analysis suggested RWMA in an extra 9 patients. Detection of regional wall motion abnormality using quantitative strain analysis was associated with a higher mean stenosis grade (P=.04) and reduced graft survival (P=.04) compared to those with no quantitative wall motion abnormality. Overall, only longitudinal stain was abnormal in patients compared with controls, but there was no correlation between any of the global indices of S or SR and IVUS measurements. CMR is more sensitive than Echo for the visual detection of significant WMAs. Quantitative CMR strain analysis at rest may give additional information to discriminate those at greatest risk.

Arterial stiffening is a heritable trait associated with arterial dilation but not wall thickening: a longitudinal study in the twins UK cohort.

Aims: Vascular ageing is characterized by arterial stiffening, dilation, and arterial wall thickening. We investigated the extent to which these changes are related and their heritability during 5 year follow-up in the Twins UK cohort. Methods and results: Carotid-femoral pulse wave velocity (PWVcf), carotid diameter, carotid distensibility, and carotid intima-media thickness (IMT) were measured in 762 female twins (mean age 57.9 ± 8.6 years) at two time-points over an average follow-up of 4.9 ± 1.5 years. Magnetic resonance imaging (MRI) was performed in a sub-sample of 38 women to measure aortic pulse wave velocity (PWVaorta), diameter, and wall thickness. Heritability of changes in arterial wall properties was estimated using structural equation modelling. Annual increases in PWVcf, carotid diameter, distensibility, and IMT were 0.139 m/s, 0.028 mm, -0.4 kPa-1, and 0.011 mm per year, respectively. In regression analysis, predictors of progression in PWVcf included age, mean arterial pressure (MAP), and heart rate (HR) at baseline, and progression in MAP, HR, and body mass index (BMI). Predictors of progression in IMT included progression in MAP, BMI, and triglyceride levels. Progression of PWV and distensibility correlated with progression in carotid diameter but not with IMT. Heritability of progression of PWVcf, diameter, and IMT was 55%, 21%, and 8%, respectively. In a sub-sample of women that underwent MRI, aortic wall thickness increased by 0.19 mm/year, but aortic wall thickening was not correlated with an increase in lumen diameter or PWVaorta. Conclusion: Arterial stiffening, as measured by PWVcf, and dilation are heritable but independent of arterial wall thickening. Genetic and cardiovascular risk factors contribute differently to progression of PWV and IMT.

Improved coronary magnetic resonance angiography using gadobenate dimeglumine in pediatric congenital heart disease.

BACKGROUND: CMRA in pediatrics remains challenging due to the smaller vessel size, high heart rates (HR), potential image degradation caused by limited patient cooperation and long acquisition times. High-relaxivity contrast agents have been shown to improve coronary imaging in adults, but limited data is available in children. We sought to investigate whether gadobenate dimeglumine (Gd-BOPTA) together with self-navigated inversion-prepared coronary magnetic resonance angiography (CMRA) sequence design improves coronary image quality in pediatric patients. METHODS: Forty consecutive patients (mean age 6±2.8years; 73% males) were prospectively recruited for a 1.5-T MRI study under general anesthesia. Two electrocardiographic-triggered free breathing steady-state free precession (SSFP) angiography sequences (A and B) with isotropic spatial resolution (1.3mm3) were acquired using a recently developed image-based self-navigation technique. Sequence A was acquired prior to contrast administration using T2 magnetization preparation (T2prep). Sequence B was acquired 5-8min after a bolus of Gd-BOPTA with the T2prep replaced by an inversion recovery (IR) pulse to null the signal from the myocardium. Scan time, signal-to noise and contrast-to-noise ratios (SNR and CNR), vessel wall sharpness (VWS) and qualitative visual score for each sequence were compared. RESULTS: Scan time was similar for both sequences (5.3±1.8 vs 5.2±1.5min, p=.532) and average heart rate (78±14.7 vs 78±14.5bpm, p=.443) remained constant throughout both acquisitions. Sequence B resulted in higher SNR (12.6±4.4 vs 31.1±7.4, p<.001) and CNR (9.0±1.8 vs 13.5±3.7, p<.001) and provided improved coronary visualization in all coronary territories (VWS A=0.53±0.07 vs B=0.56±0.07, p=.001; and visual scoring A=3.8±0.59 vs B=4.1±0.53, p<.001). The number of non-diagnostic coronary segments was lower for sequence B [A=42 (13.1%) segments vs B=33 (10.3%) segments; p=.002], and contrary to the pre-contrast sequence, never involved a proximal segment. These results were independent of the patients' age, body surface area and HR. CONCLUSIONS: The use of Gd-BOPTA with a 3D IR SSFP CMRA sequence results in improved coronary visualization in small infants and young children with high HR within a clinically acceptable scan time.

Morphological three-dimensional analysis of papillary muscles in borderline left ventricles.

OBJECTIVE: Mitral valve anatomy has a significant impact on potential surgical options for patients with hypoplastic or borderline left ventricle. Papillary muscle morphology is a major component regarding this aspect. The purpose of this study was to use cardiac magnetic resonance to describe the differences in papillary muscle anatomy between normal, borderline, and hypoplastic left ventricles. METHODS: We carried out a retrospective, observational cardiac magnetic resonance study of children (median age 5.36 years) with normal (n=30), borderline (n=22), or hypoplastic (n=13) left ventricles. Borderline and hypoplastic cases had undergone an initial hybrid procedure. Morphological features of the papillary muscles, location, and arrangement were analysed and compared across groups. RESULTS: All normal ventricles had two papillary muscles with narrow pedicles; however, 18% of borderline and 46% of hypoplastic cases had a single papillary muscle, usually the inferomedial type. In addition, in borderline or hypoplastic ventricles, the supporting pedicle occasionally displayed a wide insertion along the ventricular wall. The length ratio of the superolateral support was significantly different between groups (normal: 0.46±0.08; borderline: 0.39±0.07; hypoplastic: 0.36±0.1; p=0.009). No significant difference, however, was found when analysing the inferomedial type (0.42±0.09; 0.38±0.07; 0.39±0.22, p=0.39). The angle subtended between supports was also similar among groups (113°±17°; 111°±51° and 114°±57°; p=0.99). A total of eight children with borderline left ventricle underwent biventricular repair. There were no significant differentiating features for papillary muscle morphology in this subgroup. CONCLUSIONS: The superolateral support can be shorter or absent in borderline or hypoplastic left ventricle cases. The papillary muscle pedicles in these patients often show a broad insertion. These changes have important implications on surgical options and should be described routinely.

Aortic length measurements for pulse wave velocity calculation: manual 2D vs automated 3D centreline extraction.

BACKGROUND: Pulse wave velocity (PWV) is a biomarker for the intrinsic stiffness of the aortic wall, and has been shown to be predictive for cardiovascular events. It can be assessed using cardiovascular magnetic resonance (CMR) from the delay between phase-contrast flow waveforms at two or more locations in the aorta, and the distance on CMR images between those locations. This study aimed to investigate the impact of different distance measurement methods on PWV. We present and evaluate an algorithm for automated centreline tracking in 3D images, and compare PWV calculations using distances derived from 3D images to those obtained from a conventional 2D oblique-sagittal image of the aorta. METHODS: We included 35 patients from a twin cohort, and 20 post-coarctation repair patients. Phase-contrast flow was acquired in the ascending, descending and diaphragmatic aorta. A 3D centreline tracking algorithm is presented and evaluated on a subset of 30 subjects, on three CMR sequences: balanced steady-state free precession (SSFP), black-blood double inversion recovery turbo spin echo, and contrast-enhanced CMR angiography. Aortic lengths are subsequently compared between measurements from a 2D oblique-sagittal plane, and a 3D geometry. RESULTS: The error in length of automated 3D centreline tracking compared with manual annotations ranged from 2.4 [1.8-4.3] mm (mean [IQR], black-blood) to 6.4 [4.7-8.9] mm (SSFP). The impact on PWV was below 0.5m/s (<5%). Differences between 2D and 3D centreline length were significant for the majority of our experiments (p < 0.05). Individual differences in PWV were larger than 0.5m/s in 15% of all cases (thoracic aorta) and 37% when studying the aortic arch only. Finally, the difference between end-diastolic and end-systolic 2D centreline lengths was statistically significant (p < 0.01), but resulted in small differences in PWV (0.08 [0.04 - 0.10]m/s). CONCLUSIONS: Automatic aortic centreline tracking in three commonly used CMR sequences is possible with good accuracy. The 3D length obtained from such sequences can differ considerably from lengths obtained from a 2D oblique-sagittal plane, depending on aortic curvature, adequate planning of the oblique-sagittal plane, and patient motion between acquisitions. For accurate PWV measurements we recommend using 3D centrelines.

3D Whole Heart Imaging for Congenital Heart Disease.

Three-dimensional (3D) whole heart techniques form a cornerstone in cardiovascular magnetic resonance imaging of congenital heart disease (CHD). It offers significant advantages over other CHD imaging modalities and techniques: no ionizing radiation; ability to be run free-breathing; ECG-gated dual-phase imaging for accurate measurements and tissue properties estimation; and higher signal-to-noise ratio and isotropic voxel resolution for multiplanar reformatting assessment. However, there are limitations, such as potentially long acquisition times with image quality degradation. Recent advances in and current applications of 3D whole heart imaging in CHD are detailed, as well as future directions.

Left Atrial Performance in the Course of Hypertrophic Cardiomyopathy: Relation to Left Ventricular Hypertrophy and Fibrosis.

OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is associated with left atrial (LA) functional abnormalities. The determinants and the degree of LA dysfunction in the course of HCM are not fully understood. We aimed to characterize LA mechanics in HCM, according to the extent of left ventricular (LV) hypertrophy and fibrosis. METHODS AND RESULTS: Seventy-three HCM patients and 23 age- and sex-matched controls underwent cardiovascular magnetic resonance imaging including late gadolinium enhancement (LGE). LA reservoir, conduit, and contractile functions were quantified by fractional volume changes and cardiovascular magnetic resonance feature-tracking-derived strain and strain rate. In multivariable regression, LA mechanics were associated with the extent of LV LGE (P = 0.033 to P < 0.001), but not with the LV mass extent or maximum wall thickness (P = 0.108 to P = 0.964). Left atrial function decreased according to the increase in extent of LV fibrosis (non-LGE; mild LGE ≤ 10%; intermediate LGE 11%-19%; severe LGE ≥ 20%). Compared with healthy controls, LA conduit function was impaired in HCM with no LGE already (LA emptying fraction conduit: 32% ± 7% vs 26 ± 14, P = 0.037). Conversely, LA contractile booster pump function was impaired in HCM with severe LGE only (LA emptying fraction booster: 40% ± 8% vs 20% ± 10%, P < 0.001; for controls vs LGE ≥ 20%, respectively). CONCLUSIONS: Left atrial functional abnormalities are associated with LV fibrosis, but not with LV hypertrophy. While LA conduit function is impaired in early HCM stages as represented by mild or absent LV fibrosis, LA contractile function is impaired later in the course of disease progression as demonstrated by the presence of severe LV fibrosis only. These novel markers of LA performance may potentially proof useful for disease staging and early detection of cardiac deterioration.