Impact of training data composition on the generalizability of convolutional neural network aortic cross-section segmentation in four-dimensional magnetic resonance flow imaging.

BACKGROUND: Four-dimensional cardiovascular magnetic resonance flow imaging (4D flow CMR) plays an important role in assessing cardiovascular diseases. However, the manual or semi-automatic segmentation of aortic vessel boundaries in 4D flow data introduces variability and limits the reproducibility of aortic hemodynamics visualization and quantitative flow-related parameter computation. This paper explores the potential of deep learning to improve 4D flow CMR segmentation by developing models for automatic segmentation and analyzes the impact of the training data on the generalization of the model across different sites, scanner vendors, sequences, and pathologies. METHODS: The study population consists of 260 4D flow CMR datasets, including subjects without known aortic pathology, healthy volunteers, and patients with bicuspid aortic valve (BAV) examined at different hospitals. The dataset was split to train segmentation models on subsets with different representations of characteristics, such as pathology, gender, age, scanner model, vendor, and field strength. An enhanced three-dimensional U-net convolutional neural network (CNN) architecture with residual units was trained for time-resolved two-dimensional aortic cross-sectional segmentation. Model performance was evaluated using Dice score, Hausdorff distance, and average symmetric surface distance on test data, datasets with characteristics not represented in the training set (model-specific), and an overall evaluation set. Standard diagnostic flow parameters were computed and compared with manual segmentation results using Bland-Altman analysis and interclass correlation. RESULTS: The representation of technical factors, such as scanner vendor and field strength, in the training dataset had the strongest influence on the overall segmentation performance. Age had a greater impact than gender. Models solely trained on BAV patients' datasets performed well on datasets of healthy subjects but not vice versa. CONCLUSION: This study highlights the importance of considering a heterogeneous dataset for the training of widely applicable automatic CNN segmentations in 4D flow CMR, with a particular focus on the inclusion of different pathologies and technical aspects of data acquisition.

CARDIOKIN1: Computational Assessment of Myocardial Metabolic Capability in Healthy Controls and Patients With Valve Diseases.

BACKGROUND: Many heart diseases can result in reduced pumping capacity of the heart muscle. A mismatch between ATP demand and ATP production of cardiomyocytes is one of the possible causes. Assessment of the relation between myocardial ATP production (MVATP) and cardiac workload is important for better understanding disease development and choice of nutritional or pharmacologic treatment strategies. Because there is no method for measuring MVATP in vivo, the use of physiology-based metabolic models in conjunction with protein abundance data is an attractive approach. METHOD: We developed a comprehensive kinetic model of cardiac energy metabolism (CARDIOKIN1) that recapitulates numerous experimental findings on cardiac metabolism obtained with isolated cardiomyocytes, perfused animal hearts, and in vivo studies with humans. We used the model to assess the energy status of the left ventricle of healthy participants and patients with aortic stenosis and mitral valve insufficiency. Maximal enzyme activities were individually scaled by means of protein abundances in left ventricle tissue samples. The energy status of the left ventricle was quantified by the ATP consumption at rest (MVATP[rest]), at maximal workload (MVATP[max]), and by the myocardial ATP production reserve, representing the span between MVATP(rest) and MVATP(max). RESULTS: Compared with controls, in both groups of patients, MVATP(rest) was increased and MVATP(max) was decreased, resulting in a decreased myocardial ATP production reserve, although all patients had preserved ejection fraction. The variance of the energetic status was high, ranging from decreased to normal values. In both patient groups, the energetic status was tightly associated with mechanic energy demand. A decrease of MVATP(max) was associated with a decrease of the cardiac output, indicating that cardiac functionality and energetic performance of the ventricle are closely coupled. CONCLUSIONS: Our analysis suggests that the ATP-producing capacity of the left ventricle of patients with valvular dysfunction is generally diminished and correlates positively with mechanical energy demand and cardiac output. However, large differences exist in the energetic state of the myocardium even in patients with similar clinical or image-based markers of hypertrophy and pump function. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03172338 and NCT04068740.

Serum dihydrotestosterone levels are associated with adverse myocardial remodeling in patients with severe aortic valve stenosis before and after aortic valve replacement.

Animal studies show a pivotal role of dihydrotestosterone (DHT) in pressure overload-induced myocardial hypertrophy and dysfunction. The aim of our study was to evaluate the role of DHT levels and myocardial hypertrophy and myocardial protein expression in patients with severe aortic valve stenosis (AS). Forty-three patients [median age 68 (41-80) yr] with severe AS and indication for surgical aortic valve replacement (SAVR) were prospectively enrolled. Cardiac magnetic resonance imaging including analysis of left ventricular muscle mass (LVM), fibrosis and function, and laboratory tests including serum DHT levels were performed before and after SAVR. During SAVR, left ventricular (LV) biopsies were performed for proteomic profiling. Serum DHT levels correlated positively with indexed LVM (LVMi, R = 0.64, P = 0.0001) and fibrosis (R = 0.49, P = 0.0065) and inversely with LV function (R = -0.42, P = 0.005) in patients with severe AS. DHT levels were associated with higher abundance of the hypertrophy (moesin, R = 0.52, P = 0.0083)- and fibrosis (vimentin, R = 0.41, P = 0.039)-associated proteins from LV myocardial biopsies. Higher serum DHT levels preoperatively were associated with reduced LV function (ejection fraction, R = -0.34, P = 0.035; circulatory efficiency, R = -0.46, P = 0.012; and global longitudinal strain, R = 0.49, P = 0.01) and increased fibrosis (R = 0.55, P = 0.0022) after SAVR. Serum DHT levels were associated with adverse myocardial remodeling and higher abundance in hypertrophy- and fibrosis-associated proteins in patients with severe AS. DHT may be a target to prevent or attenuate adverse myocardial remodeling in patients with pressure overload due to AS.NEW & NOTEWORTHY Serum dihydrotestosterone (DHT) levels correlated positively with the degree of hypertrophy, fibrosis, and dysfunction from cardiac magnetic resonance imaging in female and male patients with aortic valve stenosis. Left ventricular proteome profiling had been performed in this patient cohort and an association between serum DHT levels and the abundance of the hypertrophy-associated protein moesin and the fibrosis-associated protein vimentin was found.

Muscle sodium content in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

BACKGROUND: Muscle fatigue and pain are key symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Although the pathophysiology is not yet fully understood, there is ample evidence for hypoperfusion which may result in electrolyte imbalance and sodium overload in muscles. Therefore, the aim of this study was to assess levels of sodium content in muscles of patients with ME/CFS and to compare these to healthy controls. METHODS: Six female patients with ME/CFS and six age, BMI and sex matched controls underwent 23Na-MRI of the left lower leg using a clinical 3T MR scanner before and after 3 min of plantar flexion exercise. Sodium reference phantoms with solutions of 10, 20, 30 and 40 mmol/L NaCl were used for quantification. Muscle sodium content over 40 min was measured using a dedicated plugin in the open-source DICOM viewer Horos. Handgrip strength was measured and correlated with sodium content. RESULTS: Baseline tissue sodium content was higher in all 5 lower leg muscle compartments in ME/CFS compared to controls. Within the anterior extensor muscle compartment, the highest difference in baseline muscle sodium content between ME/CFS and controls was found (mean ± SD; 12.20 ± 1.66 mM in ME/CFS versus 9.38 ± 0.71 mM in controls, p = 0.0034). Directly after exercise, tissue sodium content increased in gastrocnemius and triceps surae muscles with + 30% in ME/CFS (p = 0.0005) and + 24% in controls (p = 0.0007) in the medial gastrocnemius muscle but not in the extensor muscles which were not exercised. Compared to baseline, the increase of sodium content in medial gastrocnemius muscle was stronger in ME/CFS than in controls with + 30% versus + 17% to baseline at 12 min (p = 0.0326) and + 29% versus + 16% to baseline at 15 min (p = 0.0265). Patients had reduced average handgrip strength which was associated with increased average muscle tissue sodium content (p = 0.0319, R2 = 0.3832). CONCLUSION: Muscle sodium content before and after exercise was higher in ME/CFS than in healthy controls. Furthermore, our findings indicate an inverse correlation between muscle sodium content and handgrip strength. These findings provide evidence that sodium overload may play a role in the pathophysiology of ME/CFS and may allow for potential therapeutic targeting.

Z-score mapping for standardized analysis and reporting of cardiovascular magnetic resonance modified Look-Locker inversion recovery (MOLLI) T1 data: Normal behavior and validation in patients with amyloidosis.

BACKGROUND: T1 mapping using modified Look-Locker inversion recovery (MOLLI) provides quantitative information on myocardial tissue composition. T1 results differ between sites due to variations in hardware and software equipment, limiting the comparability of results. The aim was to test if Z-scores can be used to compare the results of MOLLI T1 mapping from different cardiovascular magnetic resonance (CMR) platforms. METHODS: First, healthy subjects (n = 15) underwent 11 combinations of native short-axis T1 mapping (four CMR systems from two manufacturers at 1.5 T and 3 T, three MOLLI schemes). Mean and standard deviation (SD) of septal myocardial T1 were derived for each combination. T1 maps were transformed into Z-score maps based on mean and SD values using a prototype post-processing module. Second, Z-score mapping was applied to a validation sample of patients with cardiac amyloidosis at 1.5 T (n = 25) or 3 T (n = 13). RESULTS: In conventional T1 analysis, results were confounded by variations in field strength, MOLLI scheme, and manufacturer-specific system characteristics. Z-score-based analysis yielded consistent results without significant differences between any two of the combinations in part 1 of the study. In the validation sample, Z-score mapping differentiated between patients with cardiac amyloidosis and healthy subjects with the same diagnostic accuracy as standard T1 analysis regardless of field strength. CONCLUSIONS: T1 analysis based on Z-score mapping provides consistent results without significant differences due to field strengths, CMR systems, or MOLLI variants, and detects cardiac amyloidosis with the same diagnostic accuracy as conventional T1 analysis. Z-score mapping provides a means to compare native T1 results acquired with MOLLI across different CMR platforms.

Personalization of electro-mechanical models of the pressure-overloaded left ventricle: fitting of Windkessel-type afterload models.

Computer models of left ventricular (LV) electro-mechanics (EM) show promise as a tool for assessing the impact of increased afterload upon LV performance. However, the identification of unique afterload model parameters and the personalization of EM LV models remains challenging due to significant clinical input uncertainties. Here, we personalized a virtual cohort of N = 17 EM LV models under pressure overload conditions. A global-local optimizer was developed to uniquely identify parameters of a three-element Windkessel (Wk3) afterload model. The sensitivity of Wk3 parameters to input uncertainty and of the EM LV model to Wk3 parameter uncertainty was analysed. The optimizer uniquely identified Wk3 parameters, and outputs of the personalized EM LV models showed close agreement with clinical data in all cases. Sensitivity analysis revealed a strong dependence of Wk3 parameters on input uncertainty. However, this had limited impact on outputs of EM LV models. A unique identification of Wk3 parameters from clinical data appears feasible, but it is sensitive to input uncertainty, thus depending on accurate invasive measurements. By contrast, the EM LV model outputs were less sensitive, with errors of less than 8.14% for input data errors of 10%, which is within the bounds of clinical data uncertainty. This article is part of the theme issue 'Uncertainty quantification in cardiac and cardiovascular modelling and simulation'.

Surgical Aortic Valve Replacement: Are We Able to Improve Hemodynamic Outcome?

Aortic valve replacement (AVR) does not usually restore physiological flow profiles. Complex flow profiles are associated with aorta dilatation, ventricle remodeling, aneurysms, and development of atherosclerosis. All these affect long-term morbidity and often require reoperations. In this pilot study, we aim to investigate an ability to optimize the real surgical AVR procedure toward flow profile associated with healthy persons. Four cases of surgical AVR (two with biological and two with mechanical valve prosthesis) with available post-treatment cardiac magnetic resonance imaging (MRI), including four-dimensional flow MRI and showing abnormal complex post-treatment hemodynamics, were investigated. All cases feature complex hemodynamic outcomes associated with valve-jet eccentricity and strong secondary flow characterized by helical flow and recirculation regions. A commercial computational fluid dynamics solver was used to simulate peak systolic hemodynamics of the real post-treatment outcome using patient-specific MRI measured boundary conditions. Then, an attempt to optimize hemodynamic outcome by modifying valve size and orientation as well as ascending aorta size reduction was made. Pressure drop, wall shear stress, secondary flow degree, helicity, maximal velocity, and turbulent kinetic energy were evaluated to characterize the AVR hemodynamic outcome. The proposed optimization strategy was successful in three of four cases investigated. Although no single parameter was identified as the sole predictor for a successful flow optimization, downsizing of the ascending aorta in combination with the valve orientation was the most effective optimization approach. Simulations promise to become an effective tool to predict hemodynamic outcome. The translation of these tools requires, however, studies with a larger cohort of patients followed by a prospective clinical validation study.

Patient-specific requirements and clinical validation of MRI-based pressure mapping: A two-center study in patients with aortic coarctation.

BACKGROUND: Invasive peak-to-peak pressure gradients are the current clinical reference standard for assessing aortic coarctation. To obtain them, patients need to undergo arterial heart catheterization. Unless an intervention is performed, the procedure remains purely diagnostic, while the concomitant risks remain. PURPOSE: To validate MRI-based pressure mapping against pressure drop derived from heart catheterization and to define minimal clinical requirements. STUDY TYPE: Prospective clinical validation study. POPULATION: Twenty-seven coarctation patients with an indicated heart catheterization were enrolled at two clinical centers. MRI SEQUENCES: 1.5T including 4D velocity-encoded MRI and 3D anatomical imaging of the aorta. ASSESSMENT: Pressure drop across the stenosis was calculated by pressure mapping based on the pressure Poisson equation. Calculated pressure drops were compared with catheter measured data. Spatial and temporal resolution were analyzed using in silico phantom-based data as well as in vivo measurements. STATISTICS: Pressure drop was compared to peak-to-peak measurements. A two-sample paired mean equivalence test was used. RESULTS: In patients without imaging artifacts and a required spatial resolution ≥5 voxel/diameter, significant equivalence of pressure mapping compared to heart catheterization was found (17.5 ± 6.49 vs. 16.6 ± 6.53 mmHg, P < 0.001). DATA CONCLUSION: Pressure mapping provides equivalent accuracy to pressure drop obtained from heart catheterization in patients 1) without previous stenting and 2) with sufficient spatial image resolution (at least 5 voxels/diameter). In these patients the method can reliably be performed prior to the actual procedure, and thus allows safe noninvasive treatment planning based on MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:81-89.

The growth and evolution of cardiovascular magnetic resonance: a 20-year history of the Society for Cardiovascular Magnetic Resonance (SCMR) annual scientific sessions.

BACKGROUND AND PURPOSE: The purpose of this work is to summarize cardiovascular magnetic resonance (CMR) research trends and highlights presented at the annual Society for Cardiovascular Magnetic Resonance (SCMR) scientific sessions over the past 20 years. METHODS: Scientific programs from all SCMR Annual Scientific Sessions from 1998 to 2017 were obtained. SCMR Headquarters also provided data for the number and the country of origin of attendees and the number of accepted abstracts according to type. Data analysis included text analysis (key word extraction) and visualization by 'word clouds' representing the most frequently used words in session titles for 5-year intervals. In addition, session titles were sorted into 17 major subject categories to further evaluate research and clinical CMR trends over time. RESULTS: Analysis of SCMR annual scientific sessions locations, attendance, and number of accepted abstracts demonstrated substantial growth of CMR research and clinical applications. As an international field of study, significant growth of CMR was documented by a strong increase in SCMR scientific session attendance (> 500%, 270 to 1406 from 1998 to 2017, number of accepted abstracts (> 700%, 98 to 701 from 1998 to 2018) and number of international participants (42-415% increase for participants from Asia, Central and South America, Middle East and Africa in 2004-2017). 'Word clouds' based evaluation of research trends illustrated a shift from early focus on 'MRI technique feasibility' to new established techniques (e.g. late gadolinium enhancement) and their clinical applications and translation (key words 'patient', 'disease') and more recently novel techniques and quantitative CMR imaging (key words 'mapping', 'T1', 'flow', 'function'). Nearly every topic category demonstrated an increase in the number of sessions over the 20-year period with 'Clinical Practice' leading all categories. Our analysis identified three growth areas 'Congenital', 'Clinical Practice', and 'Structure/function/flow'. CONCLUSION: The analysis of the SCMR historical archives demonstrates a healthy and internationally active field of study which continues to undergo substantial growth and expansion into new and emerging CMR topics and clinical application areas.

Hemodynamic Evaluation of a Biological and Mechanical Aortic Valve Prosthesis Using Patient-Specific MRI-Based CFD.

Modeling different treatment options before a procedure is performed is a promising approach for surgical decision making and patient care in heart valve disease. This study investigated the hemodynamic impact of different prostheses through patient-specific MRI-based CFD simulations. Ten time-resolved MRI data sets with and without velocity encoding were obtained to reconstruct the aorta and set hemodynamic boundary conditions for simulations. Aortic hemodynamics after virtual valve replacement with a biological and mechanical valve prosthesis were investigated. Wall shear stress (WSS), secondary flow degree (SFD), transvalvular pressure drop (TPD), turbulent kinetic energy (TKE), and normalized flow displacement (NFD) were evaluated to characterize valve-induced hemodynamics. The biological prostheses induced significantly higher WSS (medians: 9.3 vs. 8.6 Pa, P = 0.027) and SFD (means: 0.78 vs. 0.49, P = 0.002) in the ascending aorta, TPD (medians: 11.4 vs. 2.7 mm Hg, P = 0.002), TKE (means: 400 vs. 283 cm2 /s2 , P = 0.037), and NFD (means: 0.0994 vs. 0.0607, P = 0.020) than the mechanical prostheses. The differences between the prosthesis types showed great inter-patient variability, however. Given this variability, a patient-specific evaluation is warranted. In conclusion, MRI-based CFD offers an opportunity to assess the interactions between prosthesis and patient-specific boundary conditions, which may help in optimizing surgical decision making and providing additional guidance to clinicians.

Presence of reduced regional left ventricular function even in the absence of left ventricular wall scar tissue in the long term after repair of an anomalous left coronary artery from the pulmonary artery.

BACKGROUND: We sought to assess left ventricular regional function in patients with and without left ventricular wall scar tissue in the long term after repair of an anomalous origin of the left coronary artery from the pulmonary artery. METHODS: A total of 20 patients aged 12.8±7.4 years were assessed 10 (0.5-17) years after the repair of an anomalous origin of the left coronary artery from the pulmonary artery; of them, 10 (50%) patients showed left ventricular wall scar tissue on current cardiac MRI. Left ventricular regional function was assessed by two-dimensional speckle-tracking echocardiography in 10 patients with scar tissue and 10 patients without scar tissue and in 10 age-matched controls. RESULTS: In patients with scar tissue, MRI-derived left ventricular ejection fraction was significantly reduced compared with that in patients without scar tissue (51 versus 61%, p<0.05), and echocardiography-derived longitudinal strain was significantly reduced in five of six left ventricular areas compared with that in healthy controls (average relative reduction, 46%; p<0.05). In patients without scar tissue, longitudinal strain was significantly reduced in two of six left ventricular areas (average relative reduction, 23%; p<0.05) and circumferential strain was reduced in one of six left ventricular areas (relative reduction, 56%; p<0.05) compared with that in healthy controls. CONCLUSIONS: Regional left ventricular function is reduced even in patients without left ventricular wall scar tissue late after successful repair of an anomalous origin of the left coronary artery from the pulmonary artery. This highlights the need for meticulous lifelong follow-up in all patients with a repaired anomalous origin of the left coronary artery from the pulmonary artery.

MRI-based computational hemodynamics in patients with aortic coarctation using the lattice Boltzmann methods: Clinical validation study.

PURPOSE: To introduce a scheme based on a recent technique in computational hemodynamics, known as the lattice Boltzmann methods (LBM), to noninvasively measure pressure gradients in patients with a coarctation of the aorta (CoA). To provide evidence on the accuracy of the proposed scheme, the computed pressure drop values are compared against those obtained using the reference standard method of catheterization. MATERIALS AND METHODS: Pre- and posttreatment LBM-based pressure gradients for 12 patients with CoA were simulated for the time point of peak systole using the open source library OpenLB. Four-dimensional (4D) flow-sensitive phase-contrast MRI at 1.5 Tesla was used to acquire flow and to setup the simulation. The vascular geometry was reconstructed using 3D whole-heart MRI. Patients underwent pre- and postinterventional pressure catheterization as a reference standard. RESULTS: There is a significant linear correlation between the pretreatment catheter pressure drops and those computed based on the LBM simulation, r=.85, P<.001. The bias was -0.58 ± 4.1 mmHg and was not significant ( P=0.64) with a 95% confidence interval (CI) of -3.22 to 2.06. For the posttreatment results, the bias was larger and at -2.54 ± 3.53 mmHg with a 95% CI of -0.17 to -4.91 mmHg. CONCLUSION: The results indicate a reasonable agreement between the simulation results and the catheter measurements. LBM-based computational hemodynamics can be considered as an alternative to more traditional computational fluid dynamics schemes for noninvasive pressure calculations and can assist in diagnosis and therapy planning. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:139-146.

Avoidable costs of stenting for aortic coarctation in the United Kingdom: an economic model.

BACKGROUND: Undesirable outcomes in health care are associated with patient harm and substantial excess costs. Coarctation of the aorta (CoA), one of the most common congenital heart diseases, can be repaired with stenting but requires monitoring and subsequent interventions to detect and treat disease recurrence and aortic wall injuries. Avoidable costs associated with stenting in patients with CoA are unknown. METHODS: We developed an economic model to calculate potentially avoidable costs in stenting treatment of CoA in the United Kingdom over 5 years. We calculated baseline costs for the intervention and potentially avoidable complications and follow-up interventions and compared these to the costs in hypothetical scenarios with improved treatment effectiveness and complication rates. RESULTS: Baseline costs were £16 688 ($25 182) per patient. Avoidable costs ranged from £137 ($207) per patient in a scenario assuming a 10% reduction in aortic wall injuries and reinterventions at follow-up, to £1627 ($2455) in a Best-case scenario with 100% treatment success and no complications. Overall costs in the Best-case scenario were 90.2% of overall costs at Baseline. Reintervention rate at follow-up was identified as most influential lever for overall costs. Probabilistic sensitivity analysis showed a considerable degree of uncertainty for avoidable costs with widely overlapping 95% confidence intervals. CONCLUSIONS: Significant improvements in the treatment effectiveness and reductions in complication rates are required to realize discernible cost savings. Up to 10% of total baseline costs could be avoided in the best-case scenario. This highlights the need to pursue patient-specific treatment approaches which promise optimal outcomes.

Pediatric Pulmonary Hypertension: Guidelines From the American Heart Association and American Thoracic Society.

Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, and older children and contributes to significant morbidity and mortality. However, current approaches to caring for pediatric patients with pulmonary hypertension have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a panel of experienced clinicians and clinician-scientists was assembled to review the current literature and to make recommendations on the diagnosis, evaluation, and treatment of pediatric pulmonary hypertension. This publication presents the results of extensive literature reviews, discussions, and formal scoring of recommendations for the care of children with pulmonary hypertension.

Myocardial T1 maps reflect histological findings in acute and chronic stages of myocarditis in a rat model.

BACKGROUND: Cardiovascular magnetic resonance offers both diagnostic and prognostic information in myocarditis. Using an established animal model of myocarditis, the aim of this study was to measure myocardial T1 before the onset, in the acute and in the chronic phases of the disease and to compare its course with histological and immunohistochemistry findings. METHODS: Male young Lewis rats were immunized with 0.25 mg porcine myocardial myosin into the rear footpads on day 0. Native and contrast-enhanced ECG-triggered cardiac MRI examinations were performed before immunization on day 0 and on days 14, 21 and 35. Left ventricular function, pre- and post- contrast T1 parameters and LGE images were assessed using Small animal look-locker inversion recovery (SALLI). For each of the indicated time points a minimum of 4 rats were randomly sacrificed for pathological investigations including conventional histology (HE and Sirius-Red staining) and immunohistochemistry (CD 68) investigations. RESULTS: All immunized rats developed myocarditis (morbidity 100%). Histologically we observed increased wall thickness with biventricular macrophage-rich mixed inflammatory infiltrates. All rats with a histologically severe myocarditis showed increased native T1 and decreased post-contrast T1 of the myocardium. CONCLUSIONS: The assessment of native T1 and post-contrast T1 allows accurate differentiation between healthy myocardium and myocardium with inflammation and also between the acute and chronic phases of the disease.

Patient-specific modeling of left ventricular electromechanics as a driver for haemodynamic analysis.

AIMS: Models of blood flow in the left ventricle (LV) and aorta are an important tool for analysing the interplay between LV deformation and flow patterns. Typically, image-based kinematic models describing endocardial motion are used as an input to blood flow simulations. While such models are suitable for analysing the hemodynamic status quo, they are limited in predicting the response to interventions that alter afterload conditions. Mechano-fluidic models using biophysically detailed electromechanical (EM) models have the potential to overcome this limitation, but are more costly to build and compute. We report our recent advancements in developing an automated workflow for the creation of such CFD ready kinematic models to serve as drivers of blood flow simulations. METHODS AND RESULTS: EM models of the LV and aortic root were created for four pediatric patients treated for either aortic coarctation or aortic valve disease. Using MRI, ECG and invasive pressure recordings, anatomy as well as electrophysiological, mechanical and circulatory model components were personalized. RESULTS: The implemented modeling pipeline was highly automated and allowed model construction and execution of simulations of a patient's heartbeat within 1 day. All models reproduced clinical data with acceptable accuracy. CONCLUSION: Using the developed modeling workflow, the use of EM LV models as driver of fluid flow simulations is becoming feasible. While EM models are costly to construct, they constitute an important and nontrivial step towards fully coupled electro-mechano-fluidic (EMF) models and show promise as a tool for predicting the response to interventions which affect afterload conditions.

Cardiac MRI in patients with complex CHD following primary or secondary implantation of MRI-conditional pacemaker system.

OBJECTIVES: In patients with CHD, cardiac MRI is often indicated for functional and anatomical assessment. With the recent introduction of MRI-conditional pacemaker systems, cardiac MRI has become accessible for patients with pacemakers. The present clinical study aims to evaluate safety, susceptibility artefacts, and image reading of cardiac MRI in patients with CHD and MRI-conditional pacemaker systems. Material and methods CHD patients with MRI-conditional pacemaker systems and a clinical need for cardiac MRI were examined with a 1.5-T MRI system. Lead function was tested before and after MRI. Artefacts and image readings were evaluated using a four-point grading scale. RESULTS: A total of nine patients with CHD (mean age 34.0 years, range 19.5-53.6 years) received a total of 11 cardiac MRI examinations. Owing to clinical indications, seven patients had previously been converted from conventional to MRI-conditional pacemaker systems. All MRI examinations were completed without adverse effects. Device testing immediately after MRI and at follow-up showed no alteration of pacemaker device and lead function. Clinical questions could be addressed and answered in all patients. CONCLUSION: Cardiac MRI can be performed safely with high certainty of diagnosis in CHD patients with MRI-conditional pacemaker systems. In case of clinically indicated lead and box changing, CHD patients with non-MRI-conditional pacemaker systems should be considered for complete conversion to MRI-conditional systems.

Alterations in creatine metabolism observed in experimental autoimmune myocarditis using ex vivo proton magic angle spinning MRS.

Experimental autoimmune myocarditis (EAM) in rodents is an accepted model of myocarditis and dilated cardiomyopathy (DCM). Altered metabolism is thought to play an important role in the pathogenesis of DCM and heart failure (HF). Study of the metabolism may provide new diagnostic information and insights into the mechanisms of myocarditis and HF. Proton MRS ((1)H-MRS) has not yet been used to study the changes occurring in myocarditis and subsequent HF. We aimed to explore the changes in creatine metabolism using this model and compare them with the findings in healthy animals. Myocardial function of male young Lewis rats with EAM was quantified by performing left ventricular ejection fraction (LVEF) analysis in short-axis cine images throughout the whole heart. Inflammatory cellular infiltrate was assessed by immunohistochemistry. Myocardial tissue was analyzed using ex vivo proton magic angle spinning MRS ((1)H-MAS-MRS). Myocarditis was confirmed histologically by the presence of an inflammatory cellular infiltrate and CD68 positive staining. A significant increase in the metabolic ratio of Tau/tCr (taurine/total creatine) obtained by (1)H-MAS-MRS was observed in myocarditis compared with healthy controls (21 d acute EAM, 4.38 (±0.23); 21 d control, 2.84 (±0.08); 35 d chronic EAM, 4.47 (±0.83); 35 d control, 2.59 (±0.38); P < 0.001). LVEF was reduced in diseased animals (EAM, 55.2% (±11.3%); control, 72.6% (±3.8%); P < 0.01) and correlated with Tau/tCr ratio (R = 0.937, P < 0.001). Metabolic alterations occur acutely with the development of myocarditis. Myocardial Tau/tCr ratio as detected by (1)H-MRS correlates with LVEF and is able to differentiate between healthy myocardium and myocardium from rats with EAM.

MRI-based computational fluid dynamics for diagnosis and treatment prediction: clinical validation study in patients with coarctation of aorta.

PURPOSE: To reduce the need for diagnostic catheterization and optimize treatment in a variety of congenital heart diseases, magnetic resonance imaging (MRI)-based computational fluid dynamics (CFD) is proposed. However, data about the accuracy of CFD in a clinical context are still sparse. To fill this gap, this study compares MRI-based CFD to catheterization in the coarctation of aorta (CoA) setting. MATERIALS AND METHODS: Thirteen patients with CoA were investigated by routine MRI prior to catheterization. 3D whole-heart MRI was used to reconstruct geometries and 4D flow-sensitive phase-contrast MRI was used to acquire flows. Peak systolic flows were simulated using the program FLUENT. RESULTS: Peak systolic pressure drops in CoA measured by catheterization and CFD correlated significantly for both pre- and posttreatment measurements (pre: r = 0.98, p = 0.00; post: r = 0.87, p = 0.00). The pretreatment bias was -0.5 ± 3.33 mmHg (95% confidence interval -2.55 to 1.47 mmHg). CFD predicted a reduction of the peak systolic pressure drop after treatment that ranged from 17.6 ± 5.56 mmHg to 6.7 ± 5.58 mmHg. The posttreatment bias was 3.0 ± 2.91 mmHg (95% CI -1.74 to 5.43 mmHg). CONCLUSION: Peak systolic pressure drops can be reliably calculated using MRI-based CFD in a clinical setting. Therefore, CFD might be an attractive noninvasive alternative to diagnostic catheterization.