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Background Patients with repaired Tetralogy of Fallot (rTOF) often develop cardiovascular dysfunction and require regular imaging to evaluate deterioration and time interventions such as pulmonary valve replacement. Four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) enables detailed assessment of flow characteristics in all chambers and great vessels. We performed a systematic review of intra-cardiac 4D flow applications in rTOF patients, to examine clinical utility and highlight optimal methods for evaluating rTOF patients. Methods A comprehensive literature search was undertaken in March 2020 on Google Scholar and Scopus. A modified version of the Critical Appraisal Skills Programme (CASP) tool was used to assess and score the applicability of each study. Important clinical outcomes were assessed including similarities and differences. Results Of the 635 articles identified, 26 studies met eligibility for systematic review. None of these were below 59% applicability on the modified CASP score. Studies could be broadly classified into four groups: (i) pilot studies, (ii) development of new acquisition methods, (iii) validation and (vi) identification of novel flow features. Quantitative comparison with other modalities included 2D phase contrast CMR (13 studies) and echocardiography (4 studies). The 4D flow study applications included stroke volume (18/26;69%), regurgitant fraction (16/26;62%), relative branch pulmonary artery flow(4/26;15%), systolic peak velocity (9/26;35%), systemic/pulmonary total flow ratio (6/26;23%), end diastolic and end systolic volume (5/26;19%), kinetic energy (5/26;19%) and vorticity (2/26;8%). Conclusions 4D flow CMR shows potential in rTOF assessment, particularly in retrospective valve tracking for flow evaluation, velocity profiling, intra-cardiac kinetic energy quantification, and vortex visualization. Protocols should be targeted to pathology. Prospective, randomized, multi-centered studies are required to validate these new characteristics and establish their clinical use.

Background Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular events. The influence of continuous positive airway pressure (CPAP) on cardiac function remains uncertain. Purpose To prospectively determine the effects of CPAP on cardiovascular function, as measured by cardiac magnetic resonance imaging (CMR) as a sub-study of the international SAVE trial (NCT00738179). Methods Participants with OSA and established cardiovascular disease were randomized to CPAP treatment plus usual cardiovascular care or Usual Care alone. Primary outcomes were defined as change in ventricular ejection fraction (EF) and stroke volume (SV) between baseline and 6-month follow-up both groups. Secondary outcomes included other ventricular parameters including volumes, mass, and strain, and atrial parameters. Results 140 participants were included; mean CPAP adherence in those allocated to receive the treatment was 4.31±2.45 hours per night. Most were male (91%) and had moderate-severe OSA with minimal daytime sleepiness. There were no significant differences in left or right ventricular EF between groups after 6 months of treatment. There was an 8.5 mL increase in LV SV (95% CI; [4.3–12.6], p Conclusions In the first prospective CMR imaging study of patients with OSA and cardiovascular disease, CPAP treatment did not change EF after 6 months, but did have significant effects on other parameters of cardiac function. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Respironics Foundation; Australian National Health and Medical Research; New Zealand Health Research Council

We investigated if blood flow changes induced through the presence of a stent could be detected using in vitro dynamically scaled 4D Phase-Contrast Magnetic Resonance Imaging (PC-MRI). Using idealized and patient-specific left main coronary artery bifurcations, we 3D-printed the dynamically large scaled geometries and incorporated them into a flow circuit for non-invasive acquisition with a higher effective spatial resolution. We tested the effects of using non-Newtonian and Newtonian fluids for the experiment. We also numerically simulated the same geometries in true scale for comparison using computational fluid dynamics (CFD). We found that the experimental setup increased the effective spatial resolution enough to reveal stent induced blood flow changes close to the vessel wall. Non-Newtonian fluid replicated all of the flow field well with a strong agreement with the computed flow field (R2 > 0.9). Fine flow structures were not as prominent for the Newtonian compared to non-Newtonian fluid consideration. In the patient-specific geometry, arterial non-planarity increased the difficulty to capture the near wall slow velocity changes. Findings demonstrate the potential to dynamically scale in vitro 4D MRI flow acquisition for micro blood flow considerations.

Aortic regurgitation (AR) increases the hemodynamic load on both the left ventricle (LV) and the aorta. Vasodilators and beta-blockers both reduce systemic blood pressure, but their relative effects on the LV and aortic function and aortic regurgitant fraction in chronic AR are uncertain. We aimed to compare short-term effects of losartan and metoprolol on LV and aortic function in asymptomatic patients with chronic moderate to severe AR, both at rest and during exercise, using cardiac magnetic resonance (CMR) imaging. 17 chronic AR patients were randomized to 4-6 weeks losartan followed by metoprolol, or vice versa, in a cross-over design. Aortic regurgitant fraction, aortic distensibility, pulse wave velocity and LV function were assessed at rest and after moderate exercise stress (29 ± 7 W, heart rate increase 25 ± 6 bpm) using CMR. Chronic AR patients on metoprolol had a significantly lower mean heart rate, cardiac power index and rate-pressure product, than on losartan (all p

Although more patients with congenital heart disease (CHD) are now living longer due to better surgical interventions, they require regular imaging to monitor cardiac performance. There is a need for robust clinical tools which can accurately assess cardiac function of both the left and right ventricles in these patients. We have developed methods to rapidly quantify 4D (3D + time) biventricular function from standard cardiac MRI examinations. A finite element model was interactively customized to patient images using guide-point modelling. Computational efficiency and ability to model large deformations was improved by predicting cardiac motion for the left ventricle and epicardium with a polar model. In addition, large deformations through the cycle were more accurately modeled using a Cartesian deformation penalty term. The model was fitted to user-defined guide points and image feature tracking displacements throughout the cardiac cycle. We tested the methods in 60 cases comprising a variety of congenital heart diseases and showed good correlation with the gold standard manual analysis, with acceptable inter-observer error. The algorithm was considerably faster than standard analysis and shows promise as a clinical tool for patients with CHD.

Purpose To provide regional strain and ventricular volume from a single acquisition, using subtly tagged steady-state free precession (SubTag SSFP) feature tracking. Materials and Methods The effects on regional strain of tag strength in gradient recalled echo (GRE) tagging, flip angle in untagged balanced SSFP, and both in SubTag SSFP were examined in the mid left ventricle of 15 healthy volunteers at 3T. Optimal parameters were determined from varying both tag strength and SSFP flip angle using full tag saturation GRE as the reference standard. SubTag SSFP was acquired in 15 additional healthy volunteers for whole-heart volume and strain assessment using the optimized parameters. Values measured by two image analysts were compared to clinical reference standards from untagged SSFP (volumes) and GRE tagging (strains). Results Regional strain accuracy was maintained with decreasing total tagging flip angle (β); less than 3% differences for β ≥ 26°. For untagged SSFP flip angle (α), whole-wall strain differences became statistically significant when α < 40°. A SubTag SSFP acquisition with α = 40° and β = 46° showed the best combination of tagging strength, blood-myocardial contrast, and tag persistence at end-systole for regional strain estimation. SubTag SSFP also showed excellent agreement with untagged SSFP for volumetrics (percent difference: end-diastolic volume = 0.6%, end-systolic volume = 0.4%, stroke volume = 1.2%, ejection fraction = 0.6%, mass = 1.1%). Conclusion Feature tracking for regional myocardial strain assessment is dependent on image features, mainly the tag strength, persistence, and image contrast. SubTag SSFP balances these criteria to provide accurate regional strain and volumetric assessment in a single acquisition. Level of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2017.

Background Left ventricular size and shape are important for quantifying cardiac remodeling in response to cardiovascular disease. Geometric remodeling indices have been shown to have prognostic value in predicting adverse events in the clinical literature, but these often describe interrelated shape changes. We developed a novel method for deriving orthogonal remodeling components directly from any (moderately independent) set of clinical remodeling indices. Results Six clinical remodeling indices (end-diastolic volume index, sphericity, relative wall thickness, ejection fraction, apical conicity, and longitudinal shortening) were evaluated using cardiac magnetic resonance images of 300 patients with myocardial infarction, and 1991 asymptomatic subjects, obtained from the Cardiac Atlas Project. Partial least squares (PLS) regression of left ventricular shape models resulted in remodeling components that were optimally associated with each remodeling index. A Gram-Schmidt orthogonalization process, by which remodeling components were successively removed from the shape space in the order of shape variance explained, resulted in a set of orthonormal remodeling components. Remodeling scores could then be calculated that quantify the amount of each remodeling component present in each case. A one-factor PLS regression led to more decoupling between scores from the different remodeling components across the entire cohort, and zero correlation between clinical indices and subsequent scores. Conclusions The PLS orthogonal remodeling components had similar power to describe differences between myocardial infarction patients and asymptomatic subjects as principal component analysis, but were better associated with well-understood clinical indices of cardiac remodeling. The data and analyses are available from www.cardiacatlas.org.

During percutaneous coronary intervention, stents are placed in narrowings of the arteries to restore normal blood flow. Despite improvements in stent design, deployment techniques and drug-eluting coatings, restenosis and stent thrombosis remain a significant problem. Population stent design based on statistical shape analysis may improve clinical outcomes. Computed tomographic (CT) coronary angiography scans from 211 patients with a zero calcium score, no stenoses and no intermediate artery, were used to create statistical shape models of 446 major coronary artery bifurcations (left main, first diagonal and obtuse marginal and right coronary crux). Coherent point drift was used for registration. Principal component analysis shape scores were tested against clinical risk factors, quantifying the importance of recognised shape features in intervention including size, angles and curvature. Significant differences were found in (1) vessel size and bifurcation angle between the left main and other bifurcations; (2) inlet and curvature angle between the right coronary crux and other bifurcations; and (3) size and bifurcation angle by sex. Hypertension, smoking history and diabetes did not appear to have an association with shape. Physiological diameter laws were compared, with the Huo-Kassab model having the best fit. Bifurcation coronary anatomy can be partitioned into clinically meaningful modes of variation showing significant shape differences. A computational atlas of normal coronary bifurcation shape, where disease is common, may aid in the design of new stents and deployment techniques, by providing data for bench-top testing and computational modelling of blood flow and vessel wall mechanics. Electronic Supplementary Material The online version of this article (doi:10.1007/s12265-016-9720-2) contains supplementary material, which is available to authorized users.

Sparsely sampled cardiac cine accelerated acquisitions show promise for faster evaluation of left-ventricular function. Myocardial strain estimation using image feature tracking methods is also becoming widespread. However, it is not known whether highly accelerated acquisitions also provide reliable feature tracking strain estimates. Twenty patients and twenty healthy volunteers were imaged with conventional 14-beat/slice cine acquisition (STD), 4× accelerated 4-beat/slice acquisition with iterative reconstruction (R4), and a 9.2× accelerated 2-beat/slice real-time acquisition with sparse sampling and iterative reconstruction (R9.2). Radial and circumferential strains were calculated using non-rigid registration in the mid-ventricle short-axis slice and inter-observer errors were evaluated. Consistency was assessed using intra-class correlation coefficients (ICC) and bias with Bland–Altman analysis. Peak circumferential strain magnitude was highly consistent between STD and R4 and R9.2 (ICC = 0.876 and 0.884, respectively). Average bias was −1.7 ± 2.0 %, p

AIMS The aim of this study was to define the shape variations, including diameters and angles, of the major coronary artery bifurcations. METHODS AND RESULTS Computed tomographic angiograms from 300 adults with a zero calcium score and no stenoses were segmented for centreline and luminal models. A computational atlas was constructed enabling automatic quantification of 3D angles, diameters and lengths of the coronary tree. The diameter (mean±SD) of the left main coronary was 3.5±0.8 mm and the length 10.5±5.3 mm. The left main bifurcation angle (distal angle or angle B) was 89±21° for cases with, and 75±23° for those without an intermediate artery (p

The hemodynamic influence of vessel shape such as bifurcation angle is not fully understood with clinical and quantitative observations being equivocal. The aim of this study is to use computational modeling to study the hemodynamic effect of shape characteristics, in particular bifurcation angle (BA), for non-stented and stented coronary arteries. Nine bifurcations with angles of 40°, 60° and 80°, representative of ±1 SD of 101 asymptomatic computed tomography angiogram cases (average age 54±8 years; 57 females), were generated for (1) a non-stented idealized, (2) stented idealized, and (3) non-stented patient-specific geometry. Only the bifurcation angle was changed while the geometries were constant to eliminate flow effects induced by other vessel shape characteristics. The commercially available Biomatrix stent was used as a template and virtually inserted into each branch, simulating the T-stenting technique. Three patient-specific geometries with additional shape variation and ±2 SD BA variation (33°, 42° and 117°) were also computed. Computational fluid dynamics (CFD) analysis was performed for all 12 geometries to simulate physiological conditions, enabling the quantification of the hemodynamic stress distributions, including a threshold analysis of adversely low and high wall shear stress (WSS), low time-averaged WSS (TAWSS), high spatial WSS gradient (WSSG) and high Oscillatory Shear Index (OSI) area. The bifurcation angle had a minor impact on the areas of adverse hemodynamics in the idealized non-stented geometries, which fully disappeared once stented and was not apparent for patient geometries. High WSS regions were located close to the carina around peak-flow, and WSSG increased significantly after stenting for the idealized bifurcations. Additional shape variations affected the hemodynamic profiles, suggesting that BA alone has little effect on a patient׳s hemodynamic profile. Incoming flow angle, diameter and tortuosity appear to have stronger effects. This suggests that other bifurcation shape characteristics and stent placement/strategy may be more important than bifurcation angle in atherosclerotic disease development, progression, and stent outcome.

Purpose To examine the feasibility of combining computational fluid dynamics (CFD) and dynamically scaled phantom phase-contrast magnetic resonance imaging (PC-MRI) for coronary flow assessment. Materials and methods Left main coronary bifurcations segmented from computed tomography with bifurcation angles of 33°, 68°, and 117° were scaled-up ∼7× and 3D printed. Steady coronary flow was reproduced in these phantoms using the principle of dynamic similarity to preserve the true-scale Reynolds number, using blood analog fluid and a pump circuit in a 3T MRI scanner. After PC-MRI acquisition, the data were segmented and coregistered to CFD simulations of identical, but true-scale geometries. Velocities at the inlet region were extracted from the PC-MRI to define the CFD inlet boundary condition. Results The PC-MRI and CFD flow data agreed well, and comparison showed: 1) small velocity magnitude discrepancies (2-8%); 2) with a Spearman's rank correlation ≥0.72; and 3) a velocity vector correlation (including direction) of r(2) ≥ 0.82. The highest agreement was achieved for high velocity regions with discrepancies being located in slow or recirculating zones with low MRI signal-to-noise ratio (SNRv ) in tortuous segments and large bifurcating vessels. Conclusion Characterization of coronary flow using a dynamically scaled PC-MRI phantom flow is feasible and provides higher resolution than current in vivo or true-scale in vitro methods, and may be used to provide boundary conditions for true-scale CFD simulations. J. MAGN. RESON. IMAGING 2016;44:983-992.

Statistical shape modeling is a powerful tool for visualizing and quantifying geometric and functional patterns of the heart. After myocardial infarction (MI), the left ventricle typically remodels in response to physiological challenges. Several methods have been proposed in the literature to describe statistical shape changes. Which method best characterizes the left ventricular remodeling after MI is an open research question. A better descriptor of remodeling is expected to provide a more accurate evaluation of disease status in MI patients. We therefore designed a challenge to test shape characterization in MI given a set of three-dimensional left ventricular surface points. The training set comprised 100 MI patients, and 100 asymptomatic volunteers (AV). The challenge was initiated in 2015 at the Statistical Atlases and Computational Models of the Heart workshop, in conjunction with the MICCAI conference. The training set with labels was provided to participants, who were asked to submit the likelihood of MI from a different (validation) set of 200 cases (100 AV and 100 MI). Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve were used as the outcome measures. The goals of this challenge were to 1) establish a common dataset for evaluating statistical shape modeling algorithms in MI, and 2) test whether statistical shape modeling provides additional information characterizing MI patients over standard clinical measures. Eleven groups with a wide variety of classification and feature extraction approaches participated in this challenge. All methods achieved excellent classification results with accuracy ranges from 0.83 to 0.98. The areas under the receiver operating characteristic curves were all above 0.90. Four methods showed significantly higher performance than standard clinical measures. The dataset and software for evaluation are available from the Cardiac Atlas Project website. 1 1 http://www.cardiacatlas.org .

Background: Cardiac Magnetic Resonance is in need of a simple and robust method for diastolic function assessment that can be done with routine protocol sequences. Objective: To develop and validate a three-dimensional (3D) model-based volumetric assessment of diastolic function using cardiac magnetic resonance (CMR) imaging and compare the results obtained with the model with those obtained by echocardiography. Methods: The study participants provided written informed consent and were included if having undergone both echocardiography and cine steady-state free precession (SSFP) CMR on the same day. Guide points at the septal and lateral mitral annulus were used to define the early longitudinal relaxation rate (E'), while a time-volume curve from the 3D model was used to assess diastolic filling parameters. We determined the correlation between 3D CMR and echocardiography and the accuracy of CMR in classifying the diastolic function grade. Results: The study included 102 subjects. The E/A ratio by CMR was positively associated with the E/A ratio by echocardiography (r = 0.71, p < 0.0001). The early diastolic relaxation velocity by tissue Doppler and longitudinal relaxation rate for the lateral mitral annulus displacement were positively associated (p = 0.007), as were the ratio between Doppler E/e' and CMR E/E' (p = 0.01). CMR-determined normalized peak E (NE) and deceleration time (DT) were able to predict diastolic dysfunction (areas under the curve [AUCs] = 0.70 and 0.72, respectively). In addition, the lateral E/E' ratio showed good utility in identifying diastolic dysfunction (AUC = 0.80). Overall, echocardiography and CMR interobserver and intraobserver agreements were excellent (intraclass correlation coefficient range 0.72 - 0.97). Conclusion: 3D modeling of standard cine CMR images was able to identify study subjects with reduced diastolic function and showed good reproducibility, suggesting a potential for a routine diastolic function assessment by CMR. Fundamento: A ressonância magnetica cardiaca necessita de um metodo simples e robusto para a avaliacao da funcao diastolica que pode ser feito com sequencias protocolares de rotina. Objetivo: Desenvolver e validar a avaliacao volumetrica da funcao diastolica atraves de um modelo tridimensional (3D) com utilizacao de imagens de ressonância magnetica cardiaca (RMC) e comparar os resultados obtidos com este modelo com os obtidos por ecocardiografia. Metodos: Os participantes do estudo assinaram um termo de consentimento e foram incluidos se tivessem sido submetidos no mesmo dia tanto a ecocardiografia quanto a cine RMC com precessao livre no estado estacionario (steady-state free precession, SSFP). Pontos-guia foram utilizados no anel mitral septal e lateral para definir a velocidade de estiramento no inicio da diastole (E'), enquanto curvas de volume-tempo do modelo 3D foram utilizadas para avaliar os parâmetros de enchimento diastolico. Foram determinadas a correlacao entre a RMC 3D e a ecocardiografia, alem da acuracia da RMC em classificar o grau de funcao diastolica. Resultados: Ao todo, 102 sujeitos foram incluidos no estudo. A razao E/A pela RMC esteve positivamente associada com a razao E/A obtida pela ecocardiografia (r = 0,71, p < 0,0001). Estiveram positivamente associadas a velocidade de relaxamento diastolico inicial ao Doppler tecidual e a velocidade de relaxamento longitudinal de deslocamento do anel mitral lateral (p = 0,007), bem como a razao entre E/e' por Doppler e E/E' pela RMC (p = 0,01). A velocidade normalizada de pico de enchimento (EM) determinada pela RMC e o tempo de desaceleracao (TD) foram capazes de predizer a disfuncao diastolica (areas sob a curva [AUCs] = 0,70 e 0,72, respectivamente). Alem disso, a razao E/E' lateral mostrou boa utilidade para a identificacao da disfuncao diastolica (AUC = 0,80). No geral, a ecocardiografia e a RMC apresentaram excelente concordância interobservador e intraobservador (coeficiente de correlacao intraclasse 0,72 - 0,97). Conclusao: Uma modelagem 3D de imagens padroes de cine RMC foi capaz de identificar os individuos do estudo com funcao diastolica reduzida e mostrou uma boa reprodutibilidade, sugerindo ter potencial na avaliacao rotineira da funcao diastolica por RMC.

To provide regional strain and ventricular volume from a single acquisition, using subtly tagged steady-state free precession (SubTag SSFP) feature tracking.The effects on regional strain of tag strength in gradient recalled echo (GRE) tagging, flip angle in untagged balanced SSFP, and both in SubTag SSFP were examined in the mid left ventricle of 15 healthy volunteers at 3T. Optimal parameters were determined from varying both tag strength and SSFP flip angle using full tag saturation GRE as the reference standard. SubTag SSFP was acquired in 15 additional healthy volunteers for whole-heart volume and strain assessment using the optimized parameters. Values measured by two image analysts were compared to clinical reference standards from untagged SSFP (volumes) and GRE tagging (strains).Regional strain accuracy was maintained with decreasing total tagging flip angle (β); less than 3% differences for β ≥ 26°. For untagged SSFP flip angle (α), whole-wall strain differences became statistically significant when α40°. A SubTag SSFP acquisition with α = 40° and β = 46° showed the best combination of tagging strength, blood-myocardial contrast, and tag persistence at end-systole for regional strain estimation. SubTag SSFP also showed excellent agreement with untagged SSFP for volumetrics (percent difference: end-diastolic volume = 0.6%, end-systolic volume = 0.4%, stroke volume = 1.2%, ejection fraction = 0.6%, mass = 1.1%).Feature tracking for regional myocardial strain assessment is dependent on image features, mainly the tag strength, persistence, and image contrast. SubTag SSFP balances these criteria to provide accurate regional strain and volumetric assessment in a single acquisition.1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2018;47:787-797.

Congenital heart disease is the most common birth defect, with an incidence of 75 in every 1000 births. As a result of improved interventions, 90% of people with congenital heart disease now survive to adulthood. They must undergo regular imaging to assess their biventricular (left and right ventricular) function. Analysis of the images is problematic due to the large variety of shapes and complex geometry. In this paper we extend a biventricular modeling method to improve the analysis of MR images from congenital heart disease patients. We used a subdivision surface method to create three customizable exemplars, representing common manifestations of anatomy, and incorporated these as priors into an interactive biventricular customization procedure. The CHD-specific priors were tested on 60 cases representing a variety of congenital heart diseases for which the gold standard manual contours were available. The introduction of multiple priors showed a significant decrease in analysis time while maintaining good correlation between the two methods (R2 >.82).

This chapter discusses coronary artery flow assessment for atherosclerosis investigations. The overall goal is to foster the reader’s understanding of coronary flow assessment with CFD and experimental MRI, including advantages, shortcomings, and potential for clinical applicability. In Section 1 , we begin by introducing coronary artery disease and how it links to local blood flow and hemodynamic parameters, before introducing strategies to investigating coronary flow for risk assessment—computational modeling and experimental studies. Both of these need the artery geometry and embedded stents to be retrieved first, as detailed in Section 2 . Section 3 details the concepts of computational coronary flow modeling with computational fluid dynamics (CFD) including the governing equations, mesh discretization, and boundary and initial conditions. Section 4 introduces experimental approaches using in vitro flow sensitive magnetic resonance imaging (MRI), including dynamic scaling for steady or transient state considerations, creation of phantom, consideration of vessel compliance and motion, non-Newtonian blood properties, and the design of an experimental circuit. Postprocessing, analysis, and comparison of both methods are explained in Section 5 , before discussion of the accuracy and reliability of the results in Section 6 . Finally, current developments, particularly patient-specific profiling, are discussed in Section 7 .