Cardiovascular Magnetic Resonance Radiomics to Identify Components of the Extracellular Matrix in Dilated Cardiomyopathy.

BACKGROUND: Current cardiovascular magnetic resonance sequences cannot discriminate between different myocardial extracellular space (ECSs), including collagen, noncollagen, and inflammation. We sought to investigate whether cardiovascular magnetic resonance radiomics analysis can distinguish between noncollagen and inflammation from collagen in dilated cardiomyopathy. METHODS: We identified data from 132 patients with dilated cardiomyopathy scheduled for an invasive septal biopsy who underwent cardiovascular magnetic resonance at 3 T. Cardiovascular magnetic resonance imaging protocol included native and postcontrast T1 mapping and late gadolinium enhancement (LGE). Radiomic features were computed from the midseptal myocardium, near the biopsy region, on native T1, extracellular volume (ECV) map, and LGE images. Principal component analysis was used to reduce the number of radiomic features to 5 principal radiomics. Moreover, a correlation analysis was conducted to identify radiomic features exhibiting a strong correlation (r>0.9) with the 5 principal radiomics. Biopsy samples were used to quantify ECS, myocardial fibrosis, and inflammation. RESULTS: Four histopathological phenotypes were identified: low collagen (n=20), noncollagenous ECS expansion (n=49), mild to moderate collagenous ECS expansion (n=42), and severe collagenous ECS expansion (n=21). Noncollagenous expansion was associated with the highest risk of myocardial inflammation (65%). Although native T1 and ECV provided high diagnostic performance in differentiating severe fibrosis (C statistic, 0.90 and 0.90, respectively), their performance in differentiating between noncollagen and mild to moderate collagenous expansion decreased (C statistic: 0.59 and 0.55, respectively). Integration of ECV principal radiomics provided better discrimination and reclassification between noncollagen and mild to moderate collagen (C statistic, 0.79; net reclassification index, 0.83 [95% CI, 0.45-1.22]; P<0.001). There was a similar trend in the addition of native T1 principal radiomics (C statistic, 0.75; net reclassification index, 0.93 [95% CI, 0.56-1.29]; P<0.001) and LGE principal radiomics (C statistic, 0.74; net reclassification index, 0.59 [95% CI, 0.19-0.98]; P=0.004). Five radiomic features per sequence were identified with correlation analysis. They showed a similar improvement in performance for differentiating between noncollagen and mild to moderate collagen (native T1, ECV, LGE C statistic, 0.75, 0.77, and 0.71, respectively). These improvements remained significant when confined to a single radiomic feature (native T1, ECV, LGE C statistic, 0.71, 0.70, and 0.64, respectively). CONCLUSIONS: Radiomic features extracted from native T1, ECV, and LGE provide incremental information that improves our capability to discriminate noncollagenous expansion from mild to moderate collagen and could be useful for detecting subtle chronic inflammation in patients with dilated cardiomyopathy.

Cardiovascular magnetic resonance characterization of myocardial tissue injury in a miniature swine model of cancer therapy-related cardiovascular toxicity.

BACKGROUND: Left ventricular ejection fraction (LVEF) is the most commonly clinically used imaging parameter for assessing cancer therapy-related cardiac dysfunction (CTRCD). However, LVEF declines may occur late, after substantial injury. This study sought to investigate cardiovascular magnetic resonance (CMR) imaging markers of subclinical cardiac injury in a miniature swine model. METHODS: Female Yucatan miniature swine (n = 14) received doxorubicin (2 mg/kg) every 3 weeks for 4 cycles. CMR, including cine, tissue characterization via T1 and T2 mapping, and late gadolinium enhancement (LGE) were performed on the same day as doxorubicin administration and 3 weeks after the final chemotherapy cycle. In addition, magnetic resonance spectroscopy (MRS) was performed during the 3 weeks after the final chemotherapy in 7 pigs. A single CMR and MRS exam were also performed in 3 Yucatan miniature swine that were age- and weight-matched to the final imaging exam of the doxorubicin-treated swine to serve as controls. CTRCD was defined as histological early morphologic changes, including cytoplasmic vacuolization and myofibrillar loss of myocytes, based on post-mortem analysis of humanely euthanized pigs after the final CMR exam. RESULTS: Of 13 swine completing 5 serial CMR scans, 10 (77%) had histological evidence of CTRCD. Three animals had neither histological evidence nor changes in LVEF from baseline. No absolute LVEF <40% or LGE was observed. Native T1, extracellular volume (ECV), and T2 at 12 weeks were significantly higher in swine with CTRCD than those without CTRCD (1178 ms vs. 1134 ms, p = 0.002, 27.4% vs. 24.5%, p = 0.03, and 38.1 ms vs. 36.4 ms, p = 0.02, respectively). There were no significant changes in strain parameters. The temporal trajectories in native T1, ECV, and T2 in swine with CTRCD showed similar and statistically significant increases. At the same time, there were no differences in their temporal changes between those with and without CTRCD. MRS myocardial triglyceride content substantially differed among controls, swine with and without CTRCD (0.89%, 0.30%, 0.54%, respectively, analysis of variance, p = 0.01), and associated with the severity of histological findings and incidence of vacuolated cardiomyocytes. CONCLUSION: Serial CMR imaging alone has a limited ability to detect histologic CTRCD beyond LVEF. Integrating MRS myocardial triglyceride content may be useful for detection of early potential CTRCD.

Scanner-Independent MyoMapNet for Accelerated Cardiac MRI T1 Mapping Across Vendors and Field Strengths.

BACKGROUND: In cardiac T1 mapping, a series of T1 -weighted (T1 w) images are collected and numerically fitted to a two or three-parameter model of the signal recovery to estimate voxel-wise T1 values. To reduce the scan time, one can collect fewer T1 w images, albeit at the cost of precision or/and accuracy. Recently, the feasibility of using a neural network instead of conventional two- or three-parameter fit modeling has been demonstrated. However, prior studies used data from a single vendor and field strength; therefore, the generalizability of the models has not been established. PURPOSE: To develop and evaluate an accelerated cardiac T1 mapping approach based on MyoMapNet, a convolution neural network T1 estimator that can be used across different vendors and field strengths by incorporating the relevant scanner information as additional inputs to the model. STUDY TYPE: Retrospective, multicenter. POPULATION: A total of 1423 patients with known or suspected cardiac disease (808 male, 57 ± 16 years), from three centers, two vendors (Siemens, Philips), and two field strengths (1.5 T, 3 T). The data were randomly split into 60% training, 20% validation, and 20% testing. FIELD STRENGTH/SEQUENCE: A 1.5 T and 3 T, Modified Look-Locker inversion recovery (MOLLI) for native and postcontrast T1 . ASSESSMENT: Scanner-independent MyoMapNet (SI-MyoMapNet) was developed by altering the deep learning (DL) architecture of MyoMapNet to incorporate scanner vendor and field strength as inputs. Epicardial and endocardial contours and blood pool (by manually drawing a large region of interest in the blood pool) of the left ventricle were manually delineated by three readers, with 2, 8, and 9 years of experience, and SI-MyoMapNet myocardial and blood pool T1 values (calculated from four T1 w images) were compared with conventional MOLLI T1 values (calculated from 8 to 11 T1 w images). STATISTICAL TESTS: Equivalency test with 95% confidence interval (CI), linear regression slope, Pearson correlation coefficient (r), Bland-Altman analysis. RESULTS: The proposed SI-MyoMapNet successfully created T1 maps. Native and postcontrast T1 values measured from SI-MyoMapNet were strongly correlated with MOLLI, despite using only four T1 w images, at both field-strengths and vendors (all r > 0.86). For native T1 , SI-MyoMapNet and MOLLI were in good agreement for myocardial and blood T1 values in institution 1 (myocardium: 5 msec, 95% CI [3, 8]; blood: -10 msec, 95%CI [-16, -4]), in institution 2 (myocardium: 6 msec, 95% CI [0, 11]; blood: 0 msec, [-18, 17]), and in institution 3 (myocardium: 7 msec, 95% CI [-8, 22]; blood: 8 msec, [-14, 30]). Similar results were observed for postcontrast T1 . DATA CONCLUSION: Inclusion of field strength and vendor as additional inputs to the DL architecture allows generalizability of MyoMapNet across different vendors or field strength. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Obesity-Related Differences in Pathomechanism and Outcomes in Patients With HFpEF: A CMR Study.

Background: Clinical significance of an integrated evaluation of epicardial adipose tissue (EAT) and the right ventricle (RV) in heart failure with preserved ejection fraction (HFpEF) is unknown. Objectives: The authors investigated the potential of EAT and RV quantification for obesity-related pathophysiology and risk stratification in obese HFpEF patients using cardiovascular magnetic resonance (CMR). Methods: A total of 150 patients (obese, body mass index ≥30 kg/m2; n = 73, nonobese, body mass index <30 kg/m2; n = 77) with a clinical diagnosis of HFpEF undergoing CMR were retrospectively identified. EAT volume surrounding both ventricles were quantified with manual delineation on cine images. Total RV volume (TRVV) was calculated as the sum of RV cavity and mass at end-diastole. The endpoint was the composite of all-cause mortality and first HF hospitalization. Results: During a median follow-up of 46 months, 39 nonobese patients (51%) and 32 obese patients (44%) experienced the endpoint. EAT was a prognostic biomarker regardless of obesity and was independently correlated with TRVV. In obese HFpEF, EAT correlated with RV longitudinal strain (r = 0.32, P = 0.006), and increased amount of EAT and TRVV was associated with greater left ventricular end-diastolic eccentric index (r = 0.36, P = 0.002). The integration of RV quantification into EAT provided improved risk stratification with a C-statistic increase from 0.70 to 0.79 in obese HFpEF. Obese patients with EAT<130 ml and TRVV<180 ml had low risk (annual event rate 3.2%), while those with increased EAT ≥130 ml and TRVV ≥180 ml had significantly higher risk (annual event rate 11.8%; P < 0.001). Conclusions: CMR quantification of EAT and RV structure provides additive risk stratification for adverse outcomes in obese HFpEF.

Improving accuracy of myocardial T1 estimation in MyoMapNet.

PURPOSE: To improve the accuracy and robustness of T1 estimation by MyoMapNet, a deep learning-based approach using 4 inversion-recovery T1 -weighted images for cardiac T1 mapping. METHODS: MyoMapNet is a fully connected neural network for T1 estimation of an accelerated cardiac T1 mapping sequence, which collects 4 T1 -weighted images by a single Look-Locker inversion-recovery experiment (LL4). MyoMapNet was originally trained using in vivo data from the modified Look-Locker inversion recovery sequence, which resulted in significant bias and sensitivity to various confounders. This study sought to train MyoMapNet using signals generated from numerical simulations and phantom MR data under multiple simulated confounders. The trained model was then evaluated by phantom data scanned using new phantom vials that differed from those used for training. The performance of the new model was compared with modified Look-Locker inversion recovery sequence and saturation-recovery single-shot acquisition for measuring native and postcontrast T1 in 25 subjects. RESULTS: In the phantom study, T1 values measured by LL4 with MyoMapNet were highly correlated with reference values from the spin-echo sequence. Furthermore, the estimated T1 had excellent robustness to changes in flip angle and off-resonance. Native and postcontrast myocardium T1 at 3 Tesla measured by saturation-recovery single-shot acquisition, modified Look-Locker inversion recovery sequence, and MyoMapNet were 1483 ± 46.6 ms and 791 ± 45.8 ms, 1169 ± 49.0 ms and 612 ± 36.0 ms, and 1443 ± 57.5 ms and 700 ± 57.5 ms, respectively. The corresponding extracellular volumes were 22.90% ± 3.20%, 28.88% ± 3.48%, and 30.65% ± 3.60%, respectively. CONCLUSION: Training MyoMapNet with numerical simulations and phantom data will improve the estimation of myocardial T1 values and increase its robustness to confounders while also reducing the overall T1 mapping estimation time to only 4 heartbeats.

An inline deep learning based free-breathing ECG-free cine for exercise cardiovascular magnetic resonance.

BACKGROUND: Exercise cardiovascular magnetic resonance (Ex-CMR) is a promising stress imaging test for coronary artery disease (CAD). However, Ex-CMR requires accelerated imaging techniques that result in significant aliasing artifacts. Our goal was to develop and evaluate a free-breathing and electrocardiogram (ECG)-free real-time cine with deep learning (DL)-based radial acceleration for Ex-CMR. METHODS: A 3D (2D + time) convolutional neural network was implemented to suppress artifacts from aliased radial cine images. The network was trained using synthetic real-time radial cine images simulated using breath-hold, ECG-gated segmented Cartesian k-space data acquired at 3 T from 503 patients at rest. A prototype real-time radial sequence with acceleration rate = 12 was used to collect images with inline DL reconstruction. Performance was evaluated in 8 healthy subjects in whom only rest images were collected. Subsequently, 14 subjects (6 healthy and 8 patients with suspected CAD) were prospectively recruited for an Ex-CMR to evaluate image quality. At rest (n = 22), standard breath-hold ECG-gated Cartesian segmented cine and free-breathing ECG-free real-time radial cine images were acquired. During post-exercise stress (n = 14), only real-time radial cine images were acquired. Three readers evaluated residual artifact level in all collected images on a 4-point Likert scale (1-non-diagnostic, 2-severe, 3-moderate, 4-minimal). RESULTS: The DL model substantially suppressed artifacts in real-time radial cine images acquired at rest and during post-exercise stress. In real-time images at rest, 89.4% of scores were moderate to minimal. The mean score was 3.3 ± 0.7, representing increased (P < 0.001) artifacts compared to standard cine (3.9 ± 0.3). In real-time images during post-exercise stress, 84.6% of scores were moderate to minimal, and the mean artifact level score was 3.1 ± 0.6. Comparison of left-ventricular (LV) measures derived from standard and real-time cine at rest showed differences in LV end-diastolic volume (3.0 mL [- 11.7, 17.8], P = 0.320) that were not significantly different from zero. Differences in measures of LV end-systolic volume (7.0 mL [- 1.3, 15.3], P < 0.001) and LV ejection fraction (- 5.0% [- 11.1, 1.0], P < 0.001) were significant. Total inline reconstruction time of real-time radial images was 16.6 ms per frame. CONCLUSIONS: Our proof-of-concept study demonstrated the feasibility of inline real-time cine with DL-based radial acceleration for Ex-CMR.

Impact of deep learning architectures on accelerated cardiac T1 mapping using MyoMapNet.

The objective of the current study was to investigate the performance of various deep learning (DL) architectures for MyoMapNet, a DL model for T1 estimation using accelerated cardiac T1 mapping from four T1 -weighted images collected after a single inversion pulse (Look-Locker 4 [LL4]). We implemented and tested three DL architectures for MyoMapNet: (a) a fully connected neural network (FC), (b) convolutional neural networks (VGG19, ResNet50), and (c) encoder-decoder networks with skip connections (ResUNet, U-Net). Modified Look-Locker inversion recovery (MOLLI) images from 749 patients at 3 T were used for training, validation, and testing. The first four T1 -weighted images from MOLLI5(3)3 and/or MOLLI4(1)3(1)2 protocols were extracted to create accelerated cardiac T1 mapping data. We also prospectively collected data from 28 subjects using MOLLI and LL4 to further evaluate model performance. Despite rigorous training, conventional VGG19 and ResNet50 models failed to produce anatomically correct T1 maps, and T1 values had significant errors. While ResUNet yielded good quality maps, it significantly underestimated T1 . Both FC and U-Net, however, yielded excellent image quality with good T1 accuracy for both native (FC/U-Net/MOLLI = 1217 ± 64/1208 ± 61/1199 ± 61 ms, all p < 0.05) and postcontrast myocardial T1 (FC/U-Net/MOLLI = 578 ± 57/567 ± 54/574 ± 55 ms, all p < 0.05). In terms of precision, the U-Net model yielded better T1 precision compared with the FC architecture (standard deviation of 61 vs. 67 ms for the myocardium for native [p < 0.05], and 31 vs. 38 ms [p < 0.05], for postcontrast). Similar findings were observed in prospectively collected LL4 data. It was concluded that U-Net and FC DL models in MyoMapNet enable fast myocardial T1 mapping using only four T1 -weighted images collected from a single LL sequence with comparable accuracy. U-Net also provides a slight improvement in precision.

Accelerated cardiac T1 mapping in four heartbeats with inline MyoMapNet: a deep learning-based T1 estimation approach.

PURPOSE: To develop and evaluate MyoMapNet, a rapid myocardial T1 mapping approach that uses fully connected neural networks (FCNN) to estimate T1 values from four T1-weighted images collected after a single inversion pulse in four heartbeats (Look-Locker, LL4). METHOD: We implemented an FCNN for MyoMapNet to estimate T1 values from a reduced number of T1-weighted images and corresponding inversion-recovery times. We studied MyoMapNet performance when trained using native, post-contrast T1, or a combination of both. We also explored the effects of number of T1-weighted images (four and five) for native T1. After rigorous training using in-vivo modified Look-Locker inversion recovery (MOLLI) T1 mapping data of 607 patients, MyoMapNet performance was evaluated using MOLLI T1 data from 61 patients by discarding the additional T1-weighted images. Subsequently, we implemented a prototype MyoMapNet and LL4 on a 3 T scanner. LL4 was used to collect T1 mapping data in 27 subjects with inline T1 map reconstruction by MyoMapNet. The resulting T1 values were compared to MOLLI. RESULTS: MyoMapNet trained using a combination of native and post-contrast T1-weighted images had excellent native and post-contrast T1 accuracy compared to MOLLI. The FCNN model using four T1-weighted images yields similar performance compared to five T1-weighted images, suggesting that four T1 weighted images may be sufficient. The inline implementation of LL4 and MyoMapNet enables successful acquisition and reconstruction of T1 maps on the scanner. Native and post-contrast myocardium T1 by MOLLI and MyoMapNet was 1170 ± 55 ms vs. 1183 ± 57 ms (P = 0.03), and 645 ± 26 ms vs. 630 ± 30 ms (P = 0.60), and native and post-contrast blood T1 was 1820 ± 29 ms vs. 1854 ± 34 ms (P = 0.14), and 508 ± 9 ms vs. 514 ± 15 ms (P = 0.02), respectively. CONCLUSION: A FCNN, trained using MOLLI data, can estimate T1 values from only four T1-weighted images. MyoMapNet enables myocardial T1 mapping in four heartbeats with similar accuracy as MOLLI with inline map reconstruction.

Discordance in Scar Detection Between Electroanatomical Mapping and Cardiac MRI in an Infarct Swine Model.

OBJECTIVES: This study sought to investigate the sensitivity of electroanatomical mapping (EAM) to detect scar as identified by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR). BACKGROUND: Previous studies have shown correlation between low voltage electrogram amplitude and myocardial scar. However, voltage amplitude is influenced by the distance between the scar and the mapping surface and its extent. The aim of this study is to examine the reliability of low voltage EAM as a surrogate for myocardial scar using LGE-derived scar as the reference. METHODS: Twelve swine underwent anterior wall infarction by occlusion of the left anterior descending artery (LAD) (n = 6) or inferior wall infarction by occlusion of the left circumflex artery (LCx) (n = 6). Subsequently, animals underwent CMR and EAM using a multielectrode mapping catheter. CMR characteristics, including wall thickness, LGE location and extent, and EAM maps, were independently analyzed, and concordance between voltage maps and CMR characteristics was assessed. RESULTS: LGE volume was similar between the LCx and LAD groups (8.5 ± 2.2 ml vs. 8.3 ± 2.5 ml, respectively; p = 0.852). LGE scarring in the LAD group was more subendocardial, affected a larger surface area, and resulted in significant wall thinning (4.88 ± 0.43 mm). LGE scarring in the LCx group extended from the endocardium to the epicardium with minimal reduction in wall thickness (scarred: 5.4 ± 0.67 mm vs. remote: 6.75 ± 0.38 mm). In all the animals in the LAD group, areas of low voltage corresponded with LGE and wall thinning, whereas only 2 of 6 animals in the LCx group had low voltage areas on EAM. Bipolar and unipolar voltage amplitudes were higher in thick inferior walls in the LCx group than in thin anterior walls in the LAD group, despite a similar LGE volume. CONCLUSIONS: Discordances between LGE-detected scar areas and low voltage areas by EAM highlighted the limitations of the current EAM system to detect scar in thick myocardial wall regions.

Aortic regurgitation assessment by cardiovascular magnetic resonance imaging and transthoracic echocardiography: intermodality disagreement impacting on prediction of post-surgical left ventricular remodeling.

Transthoracic echocardiography (TTE) is the primary clinical imaging modality for the assessment of patients with isolated aortic regurgitation (AR) in whom TTE's linear left ventricular (LV) dimension is used to assess disease severity to guide aortic valve replacement (AVR), yet TTE is relatively limited with regards to its integrated semi-quantitative/qualitative approach. We therefore compared TTE and cardiovascular magnetic resonance (CMR) assessment of isolated AR and investigated each modality's ability to predict LV remodeling after AVR. AR severity grading by CMR and TTE were compared in 101 consecutive patients referred for CMR assessment of chronic AR. LV end-diastolic diameter and end-systolic diameter measurements by both modalities were compared. Twenty-four patients subsequently had isolated AVR. The pre-AVR estimates of regurgitation severity by CMR and TTE were correlated with favorable post-AVR LV remodeling. AR severity grade agreement between CMR and TTE was moderate (ρ = 0.317, P = 0.001). TTE underestimated CMR LV end-diastolic and LV end-systolic diameter by 6.6 mm (P < 0.001, CI 5.8-7.7) and 5.9 mm (P < 0.001, CI 4.1-7.6), respectively. The correlation of post-AVR LV remodeling with CMR AR grade (ρ = 0.578, P = 0.004) and AR volumes (R = 0.664, P < 0.001) was stronger in comparison to TTE (ρ = 0.511, P = 0.011; R = 0.318, P = 0.2). In chronic AR, CMR provides more prognostic relevant information than TTE in assessing AR severity. CMR should be considered in the management of chronic AR patients being considered for AVR.

Cardiac MR Characterization of left ventricular remodeling in a swine model of infarct followed by reperfusion.

BACKGROUND: Myocardial infarction (MI) survivors are at risk of complications including heart failure and malignant arrhythmias. PURPOSE: We undertook serial imaging of swine following MI with the aim of characterizing the longitudinal left ventricular (LV) remodeling in a translational model of ischemia-reperfusion-mediated MI. ANIMAL MODEL: Eight Yorkshire swine underwent mid left anterior descending coronary artery balloon occlusion to create an ischemia-reperfusion experimental model of MI. FIELD STRENGTH/SEQUENCES: 1.5T Philips Achieva scanner. Serial cardiac MRI was performed at 16, 33, and 62 days post-MI, including cine imaging, native and postcontrast T1 , T2 and dark-blood late gadolinium enhanced (DB-LGE) scar imaging. ASSESSMENT: Regions of interest were selected on the parametric maps to assess native T1 and T2 in the infarct and in remote tissue. Volume of enhanced tissue, nonenhanced tissue, and gray zone were assessed from DB-LGE imaging. Volumes, cardiac function, and strain were calculated from cine imaging. STATISTICAL TESTS: Parameters estimated at more than two timepoints were compared with a one-way repeated measures analysis of variance. Parametric mapping data were analyzed using a generalized linear mixed model corrected for multiple observations. A result was considered statistically significant at P < 0.05. RESULTS: All animals developed anteroseptal akinesia and hyperenhancement on DB-LGE with a central core of nonenhancing tissue. Mean hyperenhancement volume did not change during the observation period, while the central core contracted from 2.2 ± 1.8 ml at 16 days to 0.08 ± 0.19 ml at 62 days (P = 0.008). Native T1 of ischemic myocardium increased from 1173 ± 93 msec at 16 days to 1309 ± 97 msec at 62 days (P < 0.001). Mean radial and circumferential strain rate magnitude in remote myocardium increased with time from the infarct (P < 0.05). DATE CONCLUSION: In this swine model of MI, serial quantitative cardiac MR exams allow characterization of LV remodeling and scar formation. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Left Atrial Epicardial Fat Volume Is Associated With Atrial Fibrillation: A Prospective Cardiovascular Magnetic Resonance 3D Dixon Study.

BACKGROUND: Recent studies demonstrated a strong association between atrial fibrillation (AF) and epicardial fat around the left atrium (LA). We sought to assess whether epicardial fat volume around the LA is associated with AF, and to determine the additive value of LA-epicardial fat measurements to LA structural remodeling for identifying patients with AF using 3-dimensional multi-echo Dixon fat-water separated cardiovascular magnetic resonance. METHODS AND RESULTS: A total of 105 subjects were studied: 53 patients with a history of AF and 52 age-matched patients with other cardiovascular diseases but no history of AF. The 3-dimensional multi-echo Dixon fat-water separated sequence was performed for LA-epicardial fat measurements. AF patients had significantly greater LA-epicardial fat (28.9±12.3 and 14.2±7.3 mL for AF and non-AF, respectively; P<0.001) and LA volume (110.8±38.2 and 89.7±30.3 mL for AF and non-AF, respectively; P=0.002). LA-epicardial fat adjusted for LA volume was still higher in patients with AF compared with those without AF (P<0.001). LA-epicardial fat and hypertension were independently associated with the risk of AF (odds ratio, 1.17; 95% confidence interval, 1.10%-1.25%, P<0.001, and odds ratio, 3.29; 95% confidence interval, 1.17%-9.27%, P=0.03, respectively). In multivariable logistic regression analysis adjusted for body surface area, LA-epicardial fat remained significant and an increase per mL was associated with a 42% increase in the odds of AF presence (odds ratio, 1.42; 95% confidence interval, 1.23%-1.62%, P<0.001). Combined assessment of LA-epicardial fat and LA volume provided greater discriminatory performance for detecting AF than LA volume alone (c-statistic=0.88 and 0.74, respectively, DeLong test; P<0.001). CONCLUSIONS: Cardiovascular magnetic resonance 3-dimensional Dixon-based LA-epicardial fat volume is significantly increased in AF patients. LA-epicardial fat measured by 3-dimensional Dixon provides greater performance for detecting AF beyond LA structural remodeling.

Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI).

Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic resonance (CMR). Parametric mapping with CMR now permits the routine spatial visualization and quantification of changes in myocardial composition based on changes in T1, T2, and T2*(star) relaxation times and extracellular volume (ECV). These changes include specific disease pathways related to mainly intracellular disturbances of the cardiomyocyte (e.g., iron overload, or glycosphingolipid accumulation in Anderson-Fabry disease); extracellular disturbances in the myocardial interstitium (e.g., myocardial fibrosis or cardiac amyloidosis from accumulation of collagen or amyloid proteins, respectively); or both (myocardial edema with increased intracellular and/or extracellular water). Parametric mapping promises improvements in patient care through advances in quantitative diagnostics, inter- and intra-patient comparability, and relatedly improvements in treatment. There is a multitude of technical approaches and potential applications. This document provides a summary of the existing evidence for the clinical value of parametric mapping in the heart as of mid 2017, and gives recommendations for practical use in different clinical scenarios for scientists, clinicians, and CMR manufacturers.

Improved fat water separation with water selective inversion pulse for inversion recovery imaging in cardiac MRI.

PURPOSE: To develop an improved chemical shift-based water-fat separation sequence using a water-selective inversion pulse for inversion recovery 3D contrast-enhanced cardiac magnetic resonance imaging (MRI). MATERIALS AND METHODS: In inversion recovery sequences the fat signal is substantially reduced due to the application of a nonselective inversion pulse. Therefore, for simultaneous visualization of water, fat, and myocardial enhancement in inversion recovery-based sequences such as late gadolinium enhancement imaging, two separate scans are used. To overcome this, the nonselective inversion pulse is replaced with a water-selective inversion pulse. Imaging was performed in phantoms, nine healthy subjects, and nine patients with suspected arrhythmogenic right ventricular cardiomyopathy plus one patient for tumor/mass imaging. In patients, images with conventional turbo-spin echo (TSE) with and without fat saturation were acquired prior to contrast injection for fat assessment. Subjective image scores (1 = poor, 4 = excellent) were used for image assessment. RESULTS: Phantom experiments showed a fat signal-to-noise ratio (SNR) increase between 1.7 to 5.9 times for inversion times of 150 and 300 msec, respectively. The water-selective inversion pulse retains the fat signal in contrast-enhanced cardiac MR, allowing improved visualization of fat in the water-fat separated images of healthy subjects with a score of 3.7 ± 0.6. Patient images acquired with the proposed sequence were scored higher when compared with a TSE sequence (3.5 ± 0.7 vs. 2.2 ± 0.5, P < 0.05). CONCLUSION: The water-selective inversion pulse retains the fat signal in inversion recovery-based contrast-enhanced cardiac MR, allowing simultaneous visualization of water and fat.

Resveratrol modifies risk factors for coronary artery disease in swine with metabolic syndrome and myocardial ischemia.

Resveratrol has been purported to modify risk factors for obesity and cardiovascular disease. We sought to examine the effects of resveratrol in a porcine model of metabolic syndrome and chronic myocardial ischemia. Yorkshire swine were fed either a normal diet (control), a high cholesterol diet (HCD), or a high cholesterol diet with supplemental resveratrol (HCD-R; 100mg/kg/day) for 11 weeks. After 4 weeks of diet modification a baseline cardiovascular MRI was performed and an ameroid constrictor was placed on the left circumflex coronary artery of each animal to induce chronic myocardial ischemia. At 7 weeks, a second cardiovascular MRI was performed and swine were sacrificed and myocardial tissue harvested. Resveratrol supplementation resulted in lower body mass indices, serum cholesterol, and C-reactive protein levels, improved glucose tolerance and endothelial function, and favorably augmented signaling pathways associated with myocardial metabolism. Interestingly, serum tumor necrosis factor-α levels were not influenced by resveratrol treatment. Immunoblotting for markers of metabolism demonstrated that insulin receptor substrate-1, glucose transporters 1 and 4, and phospho-AMPK were increased in the HCD-R group. Peroxisome proliferator-activated receptor γ and retinol binding protein 4 were downregulated in the HCD-R group as compared to the HCD group. Myocardial perfusion and function at rest as assessed with magnetic resonance imaging were not different between groups. By favorably influencing risk factors, resveratrol may decrease the burden of chronic metabolic disease and improve cardiovascular health.

Resveratrol improves myocardial perfusion in a swine model of hypercholesterolemia and chronic myocardial ischemia.

BACKGROUND: Resveratrol may provide protection against coronary artery disease. We hypothesized that supplemental resveratrol will improve cardiac perfusion in the ischemic territory of swine with hypercholesterolemia and chronic myocardial ischemia. METHODS AND RESULTS: Yorkshire swine were fed either a normal diet (control, n=7), a hypercholesterolemic diet (HCC, n=7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/d orally, HCRV, n=7). Four weeks later, an ameroid constrictor was placed on the left circumflex artery. Animals underwent cardiac MRI and coronary angiography 7 weeks later before euthanasia and tissue harvest. Total cholesterol was lowered about 30% in HCRV animals (P<0.001). Regional wall motion analysis demonstrated a significant decrease in inferolateral function from baseline to 7 weeks in HCC swine (P=0.04). There was no significant change in regional function in HCRV swine from baseline to 7 weeks (P=0.32). Tissue blood flow during stress was 2.8-fold greater in HCRV swine when compared with HCC swine (P=0.04). Endothelium-dependent microvascular relaxation response to Substance P was diminished in HCC swine, which was rescued by resveratrol treatment (P=0.004). Capillary density (PECAM-1 staining) demonstrated fewer capillaries in both HCC and HCRV swine versus control swine (P=0.02). Immunoblot analysis demonstrated significantly greater expression in HCRV versus HCC swine of the following markers of angiogenesis: VEGF (P=0.002), peNOS (ser1177) (P=0.04), NFkB (P=0.004), and pAkt (thr308) (P=0.001). CONCLUSIONS: Supplemental resveratrol attenuates regional wall motion abnormalities, improves myocardial perfusion in the collateral dependent region, preserves endothelium-dependent coronary vessel function, and upregulates markers of angiogenesis associated with the VEGF signaling pathway.

Anti-angiogenic effect of high-dose resveratrol in a swine model of metabolic syndrome.

BACKGROUND: Resveratrol has been reported to induce angiogenesis in ischemic tissue. We hypothesized that high-dose resveratrol would improve native angiogenesis in a swine model of metabolic syndrome and chronic myocardial ischemia. METHODS: Yorkshire swine were fed a normal diet (Control, n = 7), hypercholesterolemic diet (HCD, n = 7), or hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/day orally, HCD-R; n = 7) beginning 1 month prior to surgery. Chronic ischemia was created by placing an ameroid constrictor on the left circumflex coronary artery. After 7 weeks, swine underwent functional MRI, coronary angiography, and serum and heart tissue harvest for analysis. RESULTS: HCD-R animals had lower body mass index (P < .001), total cholesterol (P < .001), low-density lipoprotein (LDL; P < .001), blood glucose levels (P < .001), and systolic blood pressure (P = .03) than HCD animals. There was no difference in regional myocardial function at 7 weeks (P = .25). Coronary angiograms revealed no difference in Rentrop collateral scores (P = .68). Staining for platelet endothelial cell adhesion molecule-1 demonstrated higher capillary density in the Control group (versus HCD and HCD-R; P = .02). Immunoblotting demonstrated decreased expression of the pro-angiogenic protein vascular endothelial (VE)-cadherin (P = .002) and an increase in anti-angiogenic proteins angiostatin (P = .001) and thrombospondin (P = .02) in the HCD and HCD-R groups. Matrix metalloprotease 2 (MMP 2; P = .47) and MMP 9 (P = .12) were not different among groups. CONCLUSION: Supplemental resveratrol positively modified cardiovascular risk factors including body mass index, cholesterol, glucose tolerance, and systolic blood pressure. However, it did not increase native collateral formation in the ischemic myocardium. This may be a result of increased angiostatin and thrombospondin leading to decreased expression of VE-cadherin and other pro-angiogenic factors.

Delayed-enhancement cardiovascular magnetic resonance coronary artery wall imaging: comparison with multislice computed tomography and quantitative coronary angiography.

OBJECTIVES: We examined whether delayed-enhancement cardiovascular magnetic resonance (DE-CMR) coronary artery wall imaging correlated with atherosclerosis detected by using multislice computed tomography (MSCT) and quantitative coronary angiography (QCA). BACKGROUND: The use of DE-CMR coronary vessel wall imaging may provide a noninvasive method to assess diseased coronary vessel walls. METHODS: We performed DE-CMR coronary artery wall imaging in 14 patients with cardiovascular risk factors and 6 healthy subjects without risk factors. RESULTS: A greater prevalence of strong DE was noted with greater MSCT evidence of disease, with DE in 2 (7%) of 30 coronary segments with no plaque by MSCT, in 1 (10%) of 10 segments with noncalcified plaque on MSCT, and in 16 (36%) of 44 segments with calcifications by MSCT (p = 0.009, adjusted p = 0.035). Delayed enhancement was observed in 8 (53%) of 15 segments with >20% coronary artery stenosis by QCA but also in 12 (15%) of 80 segments without angiographically apparent coronary disease (p = 0.004, adjusted p = 0.01). CONCLUSIONS: The use of DE-CMR allowed us to identify areas of DE that correlate with severity of atherosclerosis by MSCT and QCA. This novel approach may be useful for the assessment of coronary vessel wall in patients with suspected coronary artery disease.

Coronary magnetic resonance imaging.

This article highlights the technical challenges and general imaging strategies for coronary MRI. This is followed by a review of the clinical results for the assessment of anomalous CAD, coronary artery aneurysms, native vessel integrity, and coronary artery bypass graft disease using the more commonly applied MRI methods. It concludes with a brief discussion of the advantages/disadvantages and clinical results comparing coronary MRI with multidetector CT (MDCT) coronary angiography.