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Purpose: The aim of this study was to investigate the contrast mechanisms of Contrast-enhanced steady-state free-precession (CE-SSFP) through the utilization of Bloch simulations in an experimental porcine model and in patients with acute myocardial infarction., Methods: Six pigs and ten patients with myocardial infarction underwent CMR and tissue characterization at 1.5 T whereas a Bloch simulation framework was utilized to simulate the CE-SSFP signal formation and compare it against the actual CE-SSFP signal acquired from the experimental porcine model and the patient population. The relaxation times of remote, salvaged, and infarcted myocardium were calculated after the injection of gadolinium, at the time of CE-SSFP acquisition. Simulations were performed using the same CE-SSFP pulse sequence as used on the scanner on a set of spins with the calculated relaxation times from the CMR scans., Results: The normalized signal intensities of salvaged and infarcted myocardium obtained with simulations were lower than the corresponding normalized signal intensities obtained in vivo in pigs (p < 0.05, 134% vs 153%) and in patients (p < 0.05, 126% vs 145%). The results from simulations showed a linear relationship to the results obtained in the experimental porcine model (r 2  = 0.61) and in patients (r 2  = 0.69)., Conclusion: The T1 and T2 values of remote, salvaged, and infarcted myocardium only partly explain the signal intensities in CE-SSFP images. Bloch simulations suggest that there may be more elements that contribute to the CE-SSFP contrast. Integration of other aspects of the MR experiment into the simulation model could further help to fully unravel the mechanisms of CE-SSFP., Competing Interests: Declaration of competing interest Christos G. Xanthis and Anthony H. Aletras are founders of Corsmed AB., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Quantitative cardiovascular magnetic resonance (CMR) first pass perfusion maps are conventionally acquired with 3 short-axis (SAX) views (basal, mid, and apical) in every heartbeat (3SAX/1RR). Thus, a significant part of the left ventricle (LV) myocardium, including the apex, is not covered. The aims of this study were 1) to investigate if perfusion maps acquired with 3 short-axis views sampled every other RR-interval (2RR) yield comparable quantitative measures of myocardial perfusion (MP) as 1RR and 2) to assess if acquiring 3 additional perfusion views (i.e., total of 6) every other RR-interval (2RR) increases diagnostic confidence., Methods: In 287 patients with suspected ischemic heart disease stress and rest MP were performed on clinical indication on a 1.5T MR scanner. Eighty-three patients were examined by acquiring 3 short-axis perfusion maps with 1RR sampling (3SAX/1RR); for which also 2RR maps were reconstructed. Additionally, in 103 patients 3 short-axis and 3 long-axis (LAX; 2-, 3, and 4-chamber view) perfusion maps were acquired using 2RR sampling (3SAX + 3LAX/2RR) and in 101 patients 6 short-axis perfusion maps using 2RR sampling (6SAX/2RR) were acquired. The diagnostic confidence for ruling in or out stress-induced ischemia was scored according to a Likert scale (certain ischemia [2 points], probably ischemia [1 point], uncertain [0 points], probably no ischemia [1 point], certain no ischemia [2 points])., Results: There was a strong correlation (R = 0.99) between 3SAX/1RR and 3SAX/2RR for global MP (mL/min/g). The diagnostic confidence score increased significantly when the number of perfusion views was increased from 3 to 6 (1.24 ± 0.68 vs 1.54 ± 0.64, p < 0.001 with similar increase for 3SAX+3LAX/2RR (1.29 ± 0.68 vs 1.55 ± 0.65, p < 0.001) and for 6SAX/2RR (1.19 ± 0.69 vs 1.53 ± 0.63, p < 0.001)., Conclusion: Quantitative perfusion mapping with 2RR sampling of data yields comparable perfusion values as 1RR sampling, allowing for the acquisition of additional views within the same perfusion scan. The diagnostic confidence for stress-induced ischemia increases when adding 3 additional views, short- or long axes, to the conventional 3 short-axis views. Thus, future development and clinical implementation of quantitative CMR perfusion should aim at increasing the LV coverage from the current standard using 3 short-axis views., Competing Interests: Declaration of competing interest No declaration of interest for any of the authors., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To ultimately make accurate and precise fetal noninvasive oxygen saturation (sO 2 ) measurements by T 2 -prepared bSSFP more widely available by systematically assessing error sources in order to potentially reduce perinatal mortality in cardiovascular malformations and fetal growth restriction., Methods: T 2 -prepared bSSFP data were acquired in phantoms; in flowing blood in adults in the superior sagittal sinus, ascending and descending aorta, and main pulmonary artery; and in the fetal descending aorta and umbilical vein. T 2 was assessed in relation to T 2 two- or three-parameter curve-fitting techniques, SSFP readout, refocusing time delay (τ), constant and pulsatile blood flow, and impact of T 1 recovery. Further, fetal T 2 and sO 2 variability were quantified in the descending aorta and umbilical vein in healthy fetuses and fetuses with cardiovascular malformation (gestational weeks 32-38)., Results: In phantoms, three-parameter fitting was accurate irrespective of phase FOV (<4 ms; i.e., <2%), and T 2 was overestimated (up to 23 ms/10%; p = 0.001) beyond ±30 Hz off-resonance. In the adult aorta, T 2 was underestimated during higher blood flow velocities and pulsatility for τ = 16 ms (-41 ms/-17%; p = 0.008). In fetuses, two-parameter fitting overestimated T 2 compared with three-parameter fitting (+33 ms/+18%; p = 0.03). T 2 variability was 18 ms/15% in the fetal descending aorta and 28 ms/14% in the umbilical vein. The resulting estimated sO 2 variability was ∼10% (15% of sO 2 value) in the fetal descending aorta., Conclusions: Errors due to T 2 -fitting techniques, off-resonance, flow velocity, and insufficient T 1 recovery between image acquisitions could be mitigated by using three-parameter fitting with included saturation-prepared images approximating infinite T 2 -preparation time, adequate shimming covering the fetus and placenta, and by modifying acquisition parameters. Variability in fetal blood T 2 and sO 2 , however, indicate that it is currently not feasible to use these methods for prediction of disease., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To explore a fetal 3D cardiovascular cine acquisition using a radial image acquisition and compressed-sensing reconstruction and compare image quality and scan time with conventional multislice 2D imaging., Methods: Volumetric fetal cardiac data were acquired in 26 volunteers using a radial 3D balanced SSFP pulse sequence. Cardiac gating was performed using a Doppler ultrasound device. Images were reconstructed using a parallel-imaging and compressed-sensing algorithm. Multiplanar reformatting to standard cardiac views was performed before image analysis. Clinical 2D images were used for comparison. Qualitative and quantitative image evaluation were performed by two experienced observers (scale: 1-4). Volumes, mass, and function were assessed., Results: Average scan time for the 3D imaging was 6 min, including one localizer. A 2D imaging stack covering the entire heart including localizer sequences took at least 6.5 min, depending on planning complexity. The 3D acquisition was successful in 7 of 26 subjects (27%). Overall image contrast and perceived resolution were lower in the 3D images. Nonetheless, the 3D images had, on average, a moderate cardiac diagnostic quality (median [range]: 3 [1-4]). Standard clinical 2D acquisitions had a high cardiac diagnostic quality (median [range]: 4 [3, 4]). Cardiac measurements were not different between 2D and 3D images (all p > 0.16)., Conclusion: The presented free-breathing whole-heart fetal 3D radial cine MRI acquisition and reconstruction method enables retrospective visualization of all cardiac views while keeping examination times short. This proof-of-concept work produced images with diagnostic quality, while at the same time reducing the planning complexity to a single localizer., (© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: The objective of the study was to investigate variability and agreement of the commonly used image processing method "n-SD from remote" and in particular for quantifying myocardial infarction by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). LGE-CMR in tandem with the analysis method "n-SD from remote" represents the current reference standard for infarct quantification. This analytic method utilizes regions of interest (ROIs) and defines infarct as the tissue with a set number of standard deviations (SD) above the signal intensity of remote nulled myocardium. There is no consensus on what the set number of SD is supposed to be. Little is known about how size and location of ROIs and underlying signal properties in the LGE images affect results. Furthermore, the method is frequently used elsewhere in medical imaging often without careful validation. Therefore, the usage of the "n-SD" method warrants a thorough validation., Methods: Data from 214 patients from two multi-center cardioprotection trials were included. Infarct size from different remote ROI positions, ROI size, and number of standard deviations ("n-SD") were compared with reference core lab delineations., Results: Variability in infarct size caused by varying ROI position, ROI size, and "n-SD" was 47%, 48%, and 40%, respectively. The agreement between the "n-SD from remote" method and the reference infarct size by core lab delineations was low. Optimal "n-SD" threshold computed on a slice-by-slice basis showed high variability, n = 5.3 ± 2.2., Conclusion: The "n-SD from remote" method is unreliable for infarct quantification due to high variability which depends on different placement and size of remote ROI, number "n-SD", and image signal properties related to the CMR-scanner and sequence used. Therefore, the "n-SD from remote" method should not be used, instead methods validated against an independent standard are recommended., (© 2022. The Author(s).)

Middle Eastern immigrants constitute a growing proportion of the European population and compared to native Swedes are more insulin resistant, which can contribute to atherosclerosis. Quantitative first pass perfusion (qFPP) using cardiovascular magnetic resonance (CMR) can detect early signs of cardiovascular disease (CVD). The aim was to study if myocardial perfusion differs between healthy male Middle Eastern immigrants and native male Swedes. Eighteen Iraqi- and twelve Swedish born controls, all males, never smokers with no CVD risk factors were included. Global myocardial perfusion at rest and stress was assessed using qFPP and by phase-contrast CMR imaging of coronary sinus flow. Quantitative first pass perfusion analysis (mean ± SD) demonstrated no difference at rest between Iraqi and Swedish males (0.8 ± 0.2 vs 1.0 ± 0.4 ml/min/g, P = 0.38) but lower perfusion during adenosine in Iraqi males (2.9 ± 0.7 vs 3.5 ± 0.7 ml/min/g, P = 0.02). Myocardial perfusion assessed by coronary sinus flow demonstrated similar results with no difference in resting perfusion between groups (0.7 ± 0.2 vs 0.8 ± 0.2 ml/min/g, P = 0.21) but a lower perfusion during adenosine in the Iraqi group (3.0 ± 0.2 vs 3.7 ± 0.6 ml/min/g, P = 0.01. Myocardial perfusion during adenosine stress was lower in healthy Iraqi immigrants compared to Swedish controls suggesting impaired microvascular function and risk of underestimating CVD risk in healthy individuals of Middle Eastern origin., (© 2022. The Author(s).)

Background: Fetal cardiac magnetic resonance imaging (MRI) improves the diagnosis of congenital heart defects, but is sensitive to fetal motion due to long image acquisition time. This may be overcome with faster image acquisition with low resolution, followed by image enhancement to provide clinically useful images., Purpose: To combine phase-encoding undersampling with super-resolution neural networks to achieve high-resolution fetal cine cardiac MR images with short acquisition time., Study Type: Prospective., Subjects: Twenty-eight fetuses (gestational week 36 [interquartile range 33-38 weeks])., Field Strength/sequence: 1.5 T, balanced steady-state free precession (bSSFP) cine sequence., Assessment: Images were acquired using fully sampled Doppler ultrasound-gated clinical bSSFP cine as reference, with equivalent cine sequences with decreased phase-encoding resolution (25%, 33%, and 50% of clinical standard). Two super-resolution methods based on convolutional neural networks were proposed and evaluated (phasrGAN and phasrresnet). Data were partitioned into training (36 cine slices), validation (3 cine slices), and test sets (67 cine slices) without overlap. Conventional reconstruction methods using bicubic interpolation and k-space zeropadding were used for comparison. Three blinded observers scored image quality between 1 and 10., Statistical Tests: Image scores are reported as median [interquartile range] and were compared using Mann-Whitney's nonparametric test with P < 0.05 showing statistically significant differences., Results: Both proposed methods showed no significant difference in image quality compared to clinical images (8 [7-8.5]) down to 33% (phasrGAN 8 [6.5-8]; phasrresnet 8 [7-8], all P ≥ 0.19) phase-encoding resolution, i.e., up to three times faster image acquisition, whereas bicubic interpolation and k-space zeropadding showed significantly lower quality for 33% phase-encoding resolution (both 7 [6-8])., Data Conclusion: Super-resolution enhancement can be used for fetal cine cardiac MRI to reduce image acquisition time while maintaining image quality. This may lead to an improved success rate for fetal cine MR imaging, as the impact of fetal motion is lessened by shortened acquisitions., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 2., (© 2021 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Exercise cardiovascular magnetic resonance (CMR) can unmask cardiac pathology not evident at rest. Real-time CMR in free breathing can be used, but respiratory motion may compromise quantification of left ventricular (LV) function. We aimed to develop and validate a post-processing algorithm that semi-automatically sorts real-time CMR images according to breathing to facilitate quantification of LV function in free breathing exercise. A semi-automatic algorithm utilizing manifold learning (Laplacian Eigenmaps) was developed for respiratory sorting. Feasibility was tested in eight healthy volunteers and eight patients who underwent ECG-gated and real-time CMR at rest. Additionally, volunteers performed exercise CMR at 60% of maximum heart rate. The algorithm was validated for exercise by comparing LV mass during exercise to rest. Respiratory sorting to end expiration and end inspiration (processing time 20 to 40 min) succeeded in all research participants. Bias ± SD for LV mass was 0 ± 5 g when comparing real-time CMR at rest, and 0 ± 7 g when comparing real-time CMR during exercise to ECG-gated at rest. This study presents a semi-automatic algorithm to retrospectively perform respiratory sorting in free breathing real-time CMR. This can facilitate implementation of exercise CMR with non-ECG-gated free breathing real-time imaging, without any additional physiological input., (© 2022. The Author(s).)

Background and Objective: Supervised Machine Learning techniques have shown significant potential in medical image analysis. However, the training data that need to be collected for these techniques in the field of MRI 1) may not be available, 2) may be available but the size is small, 3) may be available but not representative and 4) may be available but with weak labels. The aim of this study was to overcome these limitations through advanced MR simulations on a realistic computer model of human anatomy without using a real MRI scanner, without scanning patients and without having personnel and the associated expenses., Methods: The 4D-XCAT model was used with the coreMRI simulation platform for generating artificial short-axis MR-images for training a neural-network to automatic delineate the LV endocardium and epicardium. Its performance was assessed on real MR-images acquired from eight healthy volunteers. The neural-network was also trained on real MR-images from a publicly available dataset and its performance was assessed on the same volunteers' data., Results: The proposed solution demonstrated a performance of 94% (endocardium) and 90% DICE (epicardium) in real mid-ventricular slices, whereas a 10% addition of real MR-images in the artificial training dataset increased the performance to 97% DICE. The use of artificial MR-images that cover the entire LV yielded 85% (endocardium) and 88% DICE (epicardium) when combined with real MR data with an 80%-20% mix respectively., Conclusions: This study suggests a low-cost solution for constructing artificial training datasets for supervised learning techniques in the field of MR by using advanced MR simulations without the use of a real MRI scanner, without scanning patients and without having to use specialized personnel, such as technologists and radiologists., Competing Interests: Competing interests CGX and AHA are co-founders of Corsmed AB., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: To verify MR measurements of myocardial extracellular volume fraction (ECV) based on clinically applicable T1-mapping sequences against ECV measurements by radioisotope tracer in pigs and to relate the results to those obtained in volunteers., Methods: Between May 2016 and March 2017, 8 volunteers (25 ± 4 years, 3 female) and 8 pigs (4 female) underwent ECV assessment with SASHA, MOLLI5(3b)3, MOLLI5(3s)3, and MOLLI5s(3s)3s. Myocardial ECV was measured independently in pigs using a radioisotope tracer method., Results: In pigs, ECV in normal myocardium was not different between radioisotope (average ± standard deviation; 19 ± 2%) and SASHA (21 ± 2%; P = 0.086). ECV was higher by MOLLI5(3b)3 (26 ± 2%), MOLLI5(3s)3 (25 ± 2%), and MOLLI5s(3s)3s (25 ± 2%) compared with SASHA or radioisotope (P ≤ 0.001 for all). ECV in volunteers was higher by MOLLI5(3b)3 (26 ± 3%) and MOLLI5(3s)3 (26 ± 3%) than by SASHA (22 ± 3%; P = 0.022 and P = 0.033). No difference was found between MOLLI5s(3s)3s (25 ± 3%) and SASHA (P = 0.225). Native T1 of blood and myocardium as well as postcontrast T1 of myocardium was consistently lower using MOLLI compared with SASHA. ECV increased over time as measured by MOLLI5(3b)3 and MOLLI5(3s)3 for pigs (0.08% and 0.07%/min; P = 0.004 and P = 0.013) and by MOLLI5s(3s)3s for volunteers (0.07%/min; P = 0.032) but did not increase as measured by SASHA., Conclusion: Clinically available MOLLI and SASHA techniques can be used to accurately estimate ECV in normal myocardium where MOLLI-sequences show minor overestimation driven by underestimation of postcontrast T1 when compared with SASHA. The timing of imaging after contrast administration affected the measurement of ECV using some variants of the MOLLI sequence., (© 2019 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Fetal cardiovascular MRI complements ultrasound to assess fetal cardiovascular pathophysiology., Purpose: To develop a free-breathing method for retrospective fetal cine MRI using Doppler ultrasound (DUS) cardiac gating and tiny golden angle radial sampling (tyGRASP) for accelerated acquisition capable of detecting fetal movements for motion compensation., Study Type: Feasibility study., Subjects: Nine volunteers (gestational week 34-40). Short-axis and four-chamber views were acquired during maternal free-breathing and breath-hold., Field Strength/sequence: 1.5T cine balanced steady-state free precession., Assessment: A self-gated reconstruction method was improved for clinical application by using 1) retrospective DUS gating, and 2) motion detection and rejection/correction algorithms for compensating for fetal motion. The free-breathing reconstructions were qualitatively and quantitatively assessed, and DUS-gating was compared with self-gating in breath-hold reconstructions. A scoring of 1-4 for overall image quality, cardiac, and extracardiac diagnostic quality was used., Statistical Tests: Friedman's test was used to assess differences in qualitative scoring between observers. A Wilcoxon matched-pairs signed rank test was used to assess differences between breath-hold and free-breathing acquisitions and between observers' quantitative measurements., Results: In all cases, 111 free-breathing and 145 breath-hold acquisitions, the automatically calculated DUS-based cardiac gating signal provided reconstructions of diagnostic quality (median score 4, range 1-4). Free-breathing did not affect the DUS-based cardiac gated retrospective radial reconstruction with respect to image or diagnostic quality (all P > 0.06). Motion detection with rejection/correction in k-space produced high-quality free-breathing DUS-based reconstructions [median 3, range (2-4)], whereas free-breathing self-gated methods failed in 80 out of 88 cases to produce a stable gating signal., Data Conclusion: Free-breathing fetal cine cardiac MRI based on DUS gating and tyGRASP with motion compensation yields diagnostic images. This simplifies acquisition for the pregnant woman and thus could help increase fetal cardiac MRI acceptance in the clinic., Level of Evidence: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:260-272., (© 2019 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Introduction: Fetal cardiovascular magnetic resonance (CMR) imaging is used clinically and for research, but has been previously limited due to lack of direct gating methods. A CMR-compatible Doppler ultrasound (DUS) gating device has resolved this. However, the DUS-gating method is not validated against the current reference method for fetal phase-contrast blood flow measurements, metric optimized gating (MOG). Further, we investigated how different methods for vessel delineation affect flow volumes and observer variability in fetal flow acquisitions., Aims: To 1) validate DUS gating versus MOG for quantifying fetal blood flow; 2) assess repeatability of DUS gating; 3) assess impact of region of interest (ROI) size on flow volume; and 4) compare time-resolved and static delineations for flow volume and observer variability., Methods: Phase-contrast CMR was acquired in the fetal descending aorta (DAo) and umbilical vein by DUS gating and MOG in 22 women with singleton pregnancy in gestational week 36 0 (26 5 -40 0 ) with repeated scans in six fetuses. Impact of ROI size on measured flow was assessed for ROI:s 50-150% of the vessel diameter. Four observers from two centers provided time-resolved and static delineations. Bland-Altman analysis was used to determine agreement between both observers and methods., Results: DAo flow was 726 (348-1130) ml/min and umbilical vein flow 366 (150-782) ml/min by DUS gating. Bias±SD for DUS-gating versus MOG were - 45 ± 122 ml/min (-6 ± 15%) for DAo and 19 ± 136 ml/min (2 ± 24%) for umbilical vein flow. Repeated flow measurements in the same fetus showed similar volumes (median CoV = 11% (DAo) and 23% (umbilical vein)). Region of interest 50-150% of vessel diameter yielded flow 35-120%. Bias±SD for time-resolved versus static DUS-gated flow was 33 ± 39 ml/min (4 ± 6%) for DAo and 11 ± 84 ml/min (2 ± 15%) for umbilical vein flow., Conclusions: Quantification of blood flow in the fetal DAo and umbilical vein using DUS-gated phase-contrast CMR is feasible and agrees with the current reference method. Repeatability was generally high for CMR fetal blood flow assessment. An ROI similar to the vessel area or slightly larger is recommended. A static ROI is sufficient for fetal flow quantification using currently available CMR sequences.

Blood flow measurements in the ascending aorta and pulmonary artery from phase-contrast magnetic resonance images require accurate time-resolved vessel segmentation over the cardiac cycle. Current semi-automatic segmentation methods often involve time-consuming manual correction, relying on user experience for accurate results. The purpose of this study was to develop a semi-automatic vessel segmentation algorithm with shape constraints based on manual vessel delineations for robust segmentation of the ascending aorta and pulmonary artery, to evaluate the proposed method in healthy volunteers and patients with heart failure and congenital heart disease, to validate the method in a pulsatile flow phantom experiment, and to make the method freely available for research purposes. Algorithm shape constraints were extracted from manual reference delineations of the ascending aorta (n = 20) and pulmonary artery (n = 20) and were included in a semi-automatic segmentation method only requiring manual delineation in one image. Bias and variability (bias ± SD) for flow volume of the proposed algorithm versus manual reference delineations were 0·0 ± 1·9 ml in the ascending aorta (n = 151; seven healthy volunteers; 144 heart failure patients) and -1·7 ± 2·9 ml in the pulmonary artery (n = 40; 25 healthy volunteers; 15 patients with atrial septal defect). Interobserver bias and variability were lower (P = 0·008) for the proposed semi-automatic method (-0·1 ± 0·9 ml) compared to manual reference delineations (1·5 ± 5·1 ml). Phantom validation showed good agreement between the proposed method and timer-and-beaker flow volumes (0·4 ± 2·7 ml). In conclusion, the proposed semi-automatic vessel segmentation algorithm can be used for efficient analysis of flow and shunt volumes in the aorta and pulmonary artery., (© 2019 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

After a reperfused myocardial infarction (MI), dynamic tissue changes occur (edema, inflammation, microvascular obstruction, hemorrhage, cardiomyocyte necrosis, and ultimately replacement by fibrosis). The extension and magnitude of these changes contribute to long-term prognosis after MI. Cardiac magnetic resonance (CMR) is the gold-standard technique for noninvasive myocardial tissue characterization. CMR is also the preferred methodology for the identification of potential benefits associated with new cardioprotective strategies both in experimental and clinical trials. However, there is a wide heterogeneity in CMR methodologies used in experimental and clinical trials, including time of post-MI scan, acquisition protocols, and, more importantly, selection of endpoints. There is a need for standardization of these methodologies to improve the translation into a real clinical benefit. The main objective of this scientific expert panel consensus document is to provide recommendations for CMR endpoint selection in experimental and clinical trials based on pathophysiology and its association with hard outcomes., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: A Cloud-ORiented Engine for advanced MRI simulations (coreMRI) is presented in this study. The aim was to develop the first advanced MR simulation platform delivered as a web service through an on-demand, scalable cloud-based and GPU-based infrastructure. We hypothesized that such an online MR simulation platform could be utilized as a virtual MRI scanner but also as a cloud-based, high-performance engine for advanced MR simulations in simulation-based quantitative MR (qMR) methods., Methods and Results: The simulation framework of coreMRI was based on the solution of the Bloch equations and utilized a ground-up-approach design based on the principles already published in the literature. The development of a front-end environment allowed the connection of the end-users to the GPU-equipped instances on the cloud. The coreMRI simulation platform was based on a modular design where individual modules (such as the Gadgetron reconstruction framework and a newly developed Pulse Sequence Designer) could be inserted in the main simulation framework. Different types and sources of pulse sequences and anatomical models were utilized in this study revealing the flexibility that the coreMRI simulation platform offers to the users. The performance and scalability of coreMRI were also examined on multi-GPU configurations on the cloud, showing that a multi-GPU computer on the cloud equipped with a newer generation of GPU cards could significantly mitigate the prolonged execution times that accompany more realistic MRI and qMR simulations., Conclusions: coreMRI is available to the entire MR community, whereas its high performance and scalability allow its users to configure advanced MRI experiments without the constraints imposed by experimentation in a true MRI scanner (such as time constraint and limited availability of MR scanners), without upfront investment for purchasing advanced computer systems and without any user expertise on computer programming or MR physics. coreMRI is available to the users through the webpage https://www.coreMRI.org., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing in terests: CGX is a co-founder, board member and CEO of corsMED AB. AHA is a co-founder and board member of corsMED AB. This does not alter our adherence to PLOS ONE policies on sharing data and materials. IP protected software owned by corsMED AB or Siemens Healthcare GmbH will not be shared.

Purpose: To validate metric optimized gating phase-contrast MR (MOG PC-MR) flow measurements for a range of fetal flow velocities in phantom experiments. 2) To investigate intra- and interobserver variability for fetal flow measurements at an imaging center other than the original site., Methods: MOG PC-MR was compared to timer/beaker measurements in a pulsatile flow phantom using a heart rate (∼145 bpm), nozzle diameter (∼6 mm), and flow range (∼130-700 mL/min) similar to fetal imaging. Fifteen healthy fetuses were included for intra- and interobserver variability in the fetal descending aorta and umbilical vein., Results: Phantom MOG PC-MR flow bias and variability was 2% ± 23%. Accuracy of MOG PC-MR was degraded for flow profiles with low velocity-to-noise ratio. Intra- and interobserver coefficients of variation were 6% and 19%, respectively, for fetal descending aorta; and 10% and 17%, respectively, for the umbilical vein., Conclusion: Phantom validation showed good agreement between MOG and conventionally gated PC-MR, except for cases with low velocity-to-noise ratio, which resulted in MOG misgating and underestimated peak velocities and warranted optimization of sequence parameters to individual fetal vessels. Inter- and intraobserver variability for fetal MOG PC-MR imaging were comparable to previously reported values., (© 2018 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Importance: Cardiac magnetic resonance (CMR) imaging can identify unrecognized myocardial infarction (UMI) in the general population. Unrecognized myocardial infarction by CMR portends poor prognosis in the short term but, to our knowledge, long-term outcomes are not known., Objective: To determine the long-term outcomes of UMI by CMR compared with clinically recognized myocardial infarction (RMI) and no myocardial infarction (MI)., Design, Setting, and Participants: Participants of the population-based, prospectively enrolled ICELAND MI cohort study (aged 67-93 years) were characterized with CMR at baseline (from January 2004-January 2007) and followed up for up to 13.3 years. Kaplan-Meier time-to-event analyses and a Cox regression were used to assess the association of UMI at baseline with death and future cardiovascular events., Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were a composite of major adverse cardiac events (MACE: death, nonfatal MI, and heart failure)., Results: Of 935 participants, 452 (48.3%) were men; the mean (SD) age of participants with no MI, UMI, and RMI was 75.6 (5.3) years, 76.8 (5.2) years, and 76.8 (4.7) years, respectively. At 3 years, UMI and no MI mortality rates were similar (3%) and lower than RMI rates (9%). At 5 years, UMI mortality rates (13%) increased and were higher than no MI rates (8%) but still lower than RMI rates (19%). By 10 years, UMI and RMI mortality rates (49% and 51%, respectively) were not statistically different; both were significantly higher than no MI (30%) (P < .001). After adjusting for age, sex, and diabetes, UMI by CMR had an increased risk of death (hazard ratio [HR], 1.61; 95% CI, 1.27-2.04), MACE (HR, 1.56; 95% CI, 1.26-1.93), MI (HR, 2.09; 95% CI, 1.45-3.03), and heart failure (HR, 1.52; 95% CI, 1.09-2.14) compared with no MI and statistically nondifferent risk of death (HR, 0.99; 95% CI, 0.71-1.38) and MACE (HR, 1.23; 95% CI, 0.91-1.66) vs RMI., Conclusions and Relevance: In this study, all-cause mortality of UMI was higher than no MI, but within 10 years from baseline evaluation was equivalent with RMI. Unrecognized MI was also associated with an elevated risk of nonfatal MI and heart failure. Whether secondary prevention can alter the prognosis of UMI will require prospective testing.

Background: Cardiovascular magnetic resonance (CMR) can be used to calculate myocardial extracellular volume fraction (ECV) by relating the longitudinal relaxation rate in blood and myocardium before and after contrast-injection to hematocrit (Hct) in blood. Hematocrit is known to vary with body posture, which could affect the calculations of ECV. The aim of this study was to test the hypothesis that there is a significant increase in calculated ECV values if the Hct is sampled after the CMR examination in supine position compared to when the patient arrives at the MR department., Methods: Forty-three consecutive patients including various pathologies as well as normal findings were included in the study. Venous blood samples were drawn upon arrival to the MR department and directly after the examination with the patient remaining in supine position. A Modified Look-Locker Inversion recovery (MOLLI) protocol was used to acquire mid-ventricular short-axis images before and after contrast injection from which motion-corrected T1 maps were derived and ECV was calculated., Results: Hematocrit decreased from 44.0 ± 3.7% before to 40.6 ± 4.0% after the CMR examination (p < 0.001). This resulted in a change in calculated ECV from 24.7 ± 3.8% before to 26.2 ± 4.2% after the CMR examination (p < 0.001). All patients decreased in Hct after the CMR examination compared to before except for two patients whose Hct remained the same., Conclusion: Variability in CMR-derived myocardial ECV can be reduced by standardizing the timing of Hct measurement relative to the CMR examination. Thus, a standardized acquisition of blood sample for Hct after the CMR examination, when the patient is still in supine position, would increase the precision of ECV measurements.

Quantitative cardiovascular Magnetic Resonance Imaging techniques are gaining wide acceptance within the MR community due to their potential to diagnose non-localized disease, guide therapy and improve patient outcome. During the last decade, there has been an increasing interest for developing new techniques that allow for simultaneous quantification of both T1 and T2 maps of myocardium. Newer studies demonstrated that the incorporation of MRI simulations could yield similar results to conventional mapping techniques in the myocardium. However, these simulation-based quantitative MR techniques usually compare the in-vivo T1 estimates against less accurate T1 techniques, whereas they present inconsistencies between simulation studies, phantom and in-vivo measurements. Moreover, these studies do not investigate the effect of Magnetization Transfer on the myocardial T1 and T2 estimates but are usually validated on phantoms where the MT effect is small. The main aim of this study was to perform simultaneous mapping of the native T1 and T2 of the myocardium through the utilization of a modified MOLLI pulse sequence and the incorporation of advanced MR simulations through the SQUAREMR framework. A second aim of this study was to investigate the effect of MT on simulation-based quantitative MR techniques. A conventional MOLLI pulse sequence was modified so as to present combined high T2 sensitivity and low MT effect. The new technique was applied in healthy volunteers and demonstrated an improved T1 accuracy compared to the conventional MOLLI and a T2 accuracy similar to the one provided by the T2prep-bSSFP method. The effect of MT on T1 and T2 estimates was also investigated in the current study. Phantoms with an increasing MT effect as well as phantoms without an MT effect were included in this work whereas several variants of the modified-MOLLI that introduce different amounts of T2 modulation on the MR signal and induce different MT effects were applied on the phantoms. The proposed simulation-based quantitative MR technique for simultaneous T1 and T2 mapping of the myocardium does not require the incorporation of a complicated custom designed pulse sequence and does not require a complicated reconstruction workflow. Moreover, the current study demonstrates for the first time that MT plays an important role in the simulation-based quantitative MR studies and points out the necessity of incorporating the study of MT in future techniques., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Fetal cardiovascular magnetic resonance (CMR) imaging may provide a valuable adjunct to fetal echocardiography in the evaluation of congenital cardiovascular pathologies. However, dynamic fetal CMR is difficult due to the lack of direct in-utero cardiac gating. The aim of this study was to investigate the effectiveness of a newly developed Doppler ultrasound (DUS) device in humans for fetal CMR gating., Methods: Fifteen fetuses (gestational age 30-39 weeks) were examined using 1.5 T CMR scanners at three different imaging sites. A newly developed CMR-compatible DUS device was used to generate gating signals from fetal cardiac motion. Gated dynamic balanced steady-state free precession images were acquired in 4-chamber and short-axis cardiac views. Gating signals during data acquisition were analyzed with respect to trigger variability and sensitivity. Image quality was assessed by measuring endocardial blurring (EB) and by image evaluation using a 4-point scale. Left ventricular (LV) volumetry was performed using the single-plane ellipsoid model., Results: Gating signals from the fetal heart were detected with a variability of 26 ± 22 ms and a sensitivity of trigger detection of 96 ± 4%. EB was 2.9 ± 0.6 pixels (4-chamber) and 2.5 ± 0.1 pixels (short axis). Image quality scores were 3.6 ± 0.6 (overall), 3.4 ± 0.7 (mitral valve), 3.4 ± 0.7 (foramen ovale), 3.6 ± 0.7 (atrial septum), 3.7 ± 0.5 (papillary muscles), 3.8 ± 0.4 (differentiation myocardium/lumen), 3.7 ± 0.5 (differentiation myocardium/lung), and 3.9 ± 0.4 (systolic myocardial thickening). Inter-observer agreement for the scores was moderate to very good (kappa 0.57-0.84) for all structures. LV volumetry revealed mean values of 2.8 ± 1.2 ml (end-diastolic volume), 0.9 ± 0.4 ml (end systolic volume), 1.9 ± 0.8 ml (stroke volume), and 69.1 ± 8.4% (ejection fraction)., Conclusion: High-quality dynamic fetal CMR was successfully performed using a newly developed DUS device for direct fetal cardiac gating. This technique has the potential to improve the utility of fetal CMR in the evaluation of congenital pathologies.

Objective: Image segmentation is an essential step in quantifying the extent of reduced or absent lung function. The aim of this study is to develop and validate a new tool for automatic segmentation of lungs in ventilation and perfusion SPECT images and compare automatic and manual SPECT lung segmentations with reference computed tomography (CT) volumes., Methods: A total of 77 subjects (69 patients with obstructive lung disease, and 8 subjects without apparent perfusion of ventilation loss) performed low-dose CT followed by ventilation/perfusion (V/P) SPECT examination in a hybrid gamma camera system. In the training phase, lung shapes from the 57 anatomical low-dose CT images were used to construct two active shape models (right lung and left lung) which were then used for image segmentation. The algorithm was validated in 20 patients, comparing its results to reference delineation of corresponding CT images, and by comparing automatic segmentation to manual delineations in SPECT images., Results: The Dice coefficient between automatic SPECT delineations and manual SPECT delineations were 0.83 ± 0.04% for the right and 0.82 ± 0.05% for the left lung. There was statistically significant difference between reference volumes from CT and automatic delineations for the right (R = 0.53, p = 0.02) and left lung (R = 0.69, p < 0.001) in SPECT. There were similar observations when comparing reference volumes from CT and manual delineations in SPECT images, left lung (bias was - 10 ± 491, R = 0.60, p = 0.005) right lung (bias 36 ± 524 ml, R = 0.62, p = 0.004)., Conclusion: Automated segmentation on SPECT images are on par with manual segmentation on SPECT images. Relative large volumetric differences between manual delineations of functional SPECT images and anatomical CT images confirms that lung segmentation of functional SPECT images is a challenging task. The current algorithm is a first step towards automatic quantification of wide range of measurements.

Background: Recent studies have shown that quantification of myocardial perfusion (MP) at stress and myocardial perfusion reserve (MPR) offer additional diagnostic and prognostic information compared to qualitative and semi-quantitative assessment of myocardial perfusion distribution in patients with coronary artery disease (CAD). Technical advancements have enabled fully automatic quantification of MP using cardiovascular magnetic resonance (CMR) to be performed in-line in a clinical workflow. The aim of this study was to validate the use of the automated CMR perfusion mapping technique for quantification of MP using 13N-NH3 cardiac positron emission tomography (PET) as the reference method., Methods: Twenty-one patients with stable CAD were included in the study. All patients underwent adenosine stress and rest perfusion imaging with 13N-NH3 PET and a dual sequence, single contrast bolus CMR on the same day. Global and regional MP were quantified both at stress and rest using PET and CMR., Results: There was good agreement between global MP quantified by PET and CMR both at stress (-0.1 ± 0.5 ml/min/g) and at rest (0 ± 0.2 ml/min/g) with a strong correlation (r = 0.92, p < 0.001; y = 0.94× + 0.14). Furthermore, there was strong correlation between CMR and PET with regards to regional MP (r = 0.83, p < 0.001; y = 0.87× + 0.26) with a good agreement (-0.1 ± 0.6 ml/min/g). There was also a significant correlation between CMR and PET with regard to global and regional MPR (r = 0.69, p = 0.001 and r = 0.57, p < 0.001, respectively)., Conclusions: There is good agreement between MP quantified by 13N-NH3 PET and dual sequence, single contrast bolus CMR in patients with stable CAD. Thus, CMR is viable in clinical practice for quantification of MP.

Purpose: To develop and assess a technique for self-gated fetal cardiac cine magnetic resonance imaging (MRI) using tiny golden angle radial sampling combined with iGRASP (iterative Golden-angle RAdial Sparse Parallel) for accelerated acquisition based on parallel imaging and compressed sensing., Materials and Methods: Fetal cardiac data were acquired from five volunteers in gestational week 29-37 at 1.5T using tiny golden angles for eddy currents reduction. The acquired multicoil radial projections were input to a principal component analysis-based compression stage. The cardiac self-gating (CSG) signal for cardiac gating was extracted from the acquired radial projections and the iGRASP reconstruction procedure was applied. In all acquisitions, a total of 4000 radial spokes were acquired within a breath-hold of less than 15 seconds using a balanced steady-state free precession pulse sequence. The images were qualitatively compared by two independent observers (on a scale of 1-4) to a single midventricular cine image from metric optimized gating (MOG) and real-time acquisitions., Results: For iGRASP and MOG images, good overall image quality (2.8 ± 0.4 and 2.6 ± 1.3, respectively, for observer 1; 3.6 ± 0.5 and 3.4 ± 0.9, respectively, for observer 2) and cardiac diagnostic quality (3.8 ± 0.4 and 3.4 ± 0.9, respectively, for observer 1; 3.6 ± 0.5 and 3.6 ± 0.9, respectively, for observer 2) were obtained, with visualized myocardial thickening over the cardiac cycle and well-defined myocardial borders to ventricular lumen and liver/lung tissue. For iGRASP, MOG, and real time, left ventricular lumen diameter (14.1 ± 2.2 mm, 14.2 ± 1.9 mm, 14.7 ± 1.1 mm, respectively) and wall thickness (2.7 ± 0.3 mm, 2.6 ± 0.3 mm, 3.0 ± 0.4, respectively) showed agreement and no statistically significant difference was found (all P > 0.05). Images with iGRASP tended to have higher overall image quality scores compared with MOG and particularly real-time images, albeit not statistically significant in this feasibility study (P > 0.99 and P = 0.12, respectively)., Conclusion: Fetal cardiac cine MRI can be performed with iGRASP using tiny golden angles and CSG. Comparison with other fetal cardiac cine MRI methods showed that the proposed method produces high-quality fetal cardiac reconstructions., Level of Evidence: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:207-217., (© 2017 International Society for Magnetic Resonance in Medicine.)

Background: Accurate assessment of myocardium at risk (MaR) after acute myocardial infarction (AMI) is necessary when assessing myocardial salvage. Contrast-enhanced steady-state free precession (CE-SSFP) is a recently developed cardiovascular magnetic resonance (CMR) method for assessment of MaR up to 1 week after AMI. Our aim was to validate CE-SSFP for determination of MaR in an experimental porcine model using myocardial perfusion single-photon emission computed tomography (MPS) as a reference standard and to test the stability of MaR-quantification over time after injecting gadolinium-based contrast., Methods: Eleven pigs were subjected to either 35 or 40 min occlusion of the left anterior descending artery followed by six hours of reperfusion. A technetium-based perfusion tracer was administered intravenously ten minutes before reperfusion. In-vivo and ex-vivo CE-SSFP CMR was performed followed by ex-vivo MPS imaging. MaR was expressed as % of left ventricular mass (LVM)., Results: There was good agreement between MaR by ex-vivo CMR and MaR by MPS (bias: 1 ± 3% LVM, r 2  = 0.92, p < 0.001), between ex-vivo and in-vivo CMR (bias 0 ± 2% LVM, r 2  = 0.94, p < 0.001) and between in-vivo CMR and MPS (bias -2 ± 3% LVM, r 2  = 0.87, p < 0.001. No change in MaR was seen over the first 30 min after contrast injection (p = 0.95)., Conclusions: Contrast-enhanced SSFP cine CMR can be used to measure MaR, both in vivo and ex vivo, in a porcine model with good accuracy and precision over the first 30 min after contrast injection. This offers the option to use the less complex ex-vivo imaging when determining myocardial salvage in experimental studies.

Quantitative Magnetic Resonance Imaging (MRI) is a research tool, used more and more in clinical practice, as it provides objective information with respect to the tissues being imaged. Pixel-wise T 1 quantification (T 1 mapping) of the myocardium is one such application with diagnostic significance. A number of mapping sequences have been developed for myocardial T 1 mapping with a wide range in terms of measurement accuracy and precision. Furthermore, measurement results obtained with these pulse sequences are affected by errors introduced by the particular acquisition parameters used. SQUAREMR is a new method which has the potential of improving the accuracy of these mapping sequences through the use of massively parallel simulations on Graphical Processing Units (GPUs) by taking into account different acquisition parameter sets. This method has been shown to be effective in myocardial T 1 mapping; however, execution times may exceed 30min which is prohibitively long for clinical applications. The purpose of this study was to accelerate the construction of SQUAREMR's multi-parametric database to more clinically acceptable levels. The aim of this study was to develop a cloud-based cluster in order to distribute the computational load to several GPU-enabled nodes and accelerate SQUAREMR. This would accommodate high demands for computational resources without the need for major upfront equipment investment. Moreover, the parameter space explored by the simulations was optimized in order to reduce the computational load without compromising the T 1 estimates compared to a non-optimized parameter space approach. A cloud-based cluster with 16 nodes resulted in a speedup of up to 13.5 times compared to a single-node execution. Finally, the optimized parameter set approach allowed for an execution time of 28s using the 16-node cluster, without compromising the T 1 estimates by more than 10ms. The developed cloud-based cluster and optimization of the parameter set reduced the execution time of the simulations involved in constructing the SQUAREMR multi-parametric database thus bringing SQUAREMR's applicability within time frames that would be likely acceptable in the clinic., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Targeted therapies in connective tissue diseases (CTDs) have led to improvements of disease-associated outcomes, but life expectancy remains lower compared to general population due to emerging co-morbidities, particularly due to excess cardiovascular risk. Cardiovascular magnetic resonance (CMR) is a noninvasive imaging technique which can provide detailed information about multiple cardiovascular pathologies without using ionizing radiation. CMR is considered the reference standard for quantitative evaluation of left and right ventricular volumes, mass and function, cardiac tissue characterization and assessment of thoracic vessels; it may also be used for the quantitative assessment of myocardial blood flow with high spatial resolution and for the evaluation of the proximal coronary arteries. These applications are of particular interest in CTDs, because of the potential of serious and variable involvement of the cardiovascular system during their course. The International Consensus Group on CMR in Rheumatology was formed in January 2012 aiming to achieve consensus among CMR and rheumatology experts in developing initial recommendations on the current state-of-the-art use of CMR in CTDs. The present report outlines the recommendations of the participating CMR and rheumatology experts with regards to: (a) indications for use of CMR in rheumatoid arthritis, the spondyloarthropathies, systemic lupus erythematosus, vasculitis of small, medium and large vessels, myositis, sarcoidosis (SRC), and scleroderma (SSc); (b) CMR protocols, terminology for reporting CMR and diagnostic CMR criteria for assessment and quantification of cardiovascular involvement in CTDs; and (c) a research agenda for the further development of this evolving field., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Determination of the relaxation time constants T1 and T2 with quantitative magnetic resonance imaging is increasingly used for both research and clinical practice. Recently, groups have been formed within the Society of Cardiovascular Magnetic Resonance to address issues with relaxometry. However, so far they have avoided specific recommendations on methodology due to lack of consensus and current evolving research. Standardised widely available software may simplify this process. The purpose of the current study was to develop and validate vendor-independent T1 and T2 mapping modules and implement those in the versatile and widespread software Segment, freely available for research and FDA approved for clinical applications., Results: The T1 and T2 mapping modules were developed and validated in phantoms at 1.5 T and 3 T with reference standard values calculated from reference pulse sequences using the Nelder-Mead Simplex optimisation method. The proposed modules support current commonly available MRI pulse sequences and both 2- and 3-parameter curve fitting. Images acquired in patients using three major vendors showed vendor-independence. Bias and variability showed high agreement with T1 and T2 reference standards for T1 (range 214-1752 ms) and T2 (range 45-338 ms), respectively., Conclusions: The developed and validated T1 and T2 mapping and quantification modules generated relaxation maps from current commonly used MRI sequences and multiple signal models. Patient applications showed usability for three major vendors.

An experimental setup for characterizing the magnetic field of MRI RF coils was proposed and tested. The setup consisted of a specially configured 3D-printer, a network analyzer and a mid-performance desktop PC. The setup was tested on a single loop RF coil, part of a phased array for fetal imaging. Then, the setup was used for determining the magnetic field characteristics of a high-pass birdcage coil used for neonatal MR imaging with a vertical static field. The scattering parameter S21, converted into power ratio, was used for mapping the B1 magnetic field. The experimental measurements from the loop coil were close to the theoretical results (R=0.924). A high degree of homogeneity was measured for the neonatal birdcage RF coil. The development of MR RF coils is time consuming and resource intensive. The proposed experimental setup provides an alternative method for magnetic field characterization of RF coils used in MRI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: Myocardial salvage, determined by cardiac magnetic resonance imaging (CMR), is used as end point in cardioprotection trials. To calculate myocardial salvage, infarct size is related to myocardium at risk (MaR), which can be assessed by T2-short tau inversion recovery (T2-STIR) and contrast-enhanced steady-state free precession magnetic resonance imaging (CE-SSFP). We aimed to determine how T2-STIR and CE-SSFP perform in determining MaR when applied in multicentre, multi-vendor settings., Methods and Results: A total of 215 patients from 17 centres were included after percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction. CMR was performed within 1-8 days. These patients participated in the MITOCARE or CHILL-MI cardioprotection trials. Additionally, 8 patients from a previous study, imaged 1 day post-CMR, were included. Late gadolinium enhancement, T2-STIR, and CE-SSFP images were acquired on 1.5T MR scanners (Philips, Siemens, or GE). In 65% of the patients, T2-STIR was of diagnostic quality compared with 97% for CE-SSFP. In diagnostic quality images, there was no difference in MaR by T2-STIR and CE-SSFP (bias: 0.02 ± 6%, P = 0.96, r(2) = 0.71, P < 0.001), or between treatment and control arms. No change in size or quality of MaR nor ability to identify culprit artery was seen over the first week after the acute event (P = 0.44)., Conclusion: In diagnostic quality images, T2-STIR and CE-SSFP provide similar estimates of MaR, were constant over the first week, and were not affected by treatment. CE-SSFP had a higher degree of diagnostic quality images compared with T2 imaging for sequences from two out of three vendors. Therefore, CE-SSFP is currently more suitable for implementation in multicentre, multi-vendor clinical trials., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Contrast-enhanced steady state free precession (CE-SSFP) and T2-weighted short tau inversion recovery (T2-STIR) have been clinically validated to estimate myocardium at risk (MaR) by cardiovascular magnetic resonance while using myocardial perfusion single-photon emission computed tomography as reference standard. Myocardial perfusion single-photon emission computed tomography has been used to describe the coronary perfusion territories during myocardial ischemia. Compared with myocardial perfusion single-photon emission computed tomography, cardiovascular magnetic resonance offers superior image quality and practical advantages. Therefore, the aim was to describe the main coronary perfusion territories using CE-SSFP and T2-STIR cardiovascular magnetic resonance data in patients after acute ST-segment-elevation myocardial infarction., Methods and Results: CE-SSFP and T2-STIR data from 2 recent multicenter trials, CHILL-MI and MITOCARE (n=215), were used to assess MaR. Angiography was used to determine culprit vessel. Of 215 patients, 39% had left anterior descending artery occlusion, 49% had right coronary artery occlusion, and 12% had left circumflex artery occlusion. Mean extent of MaR using CE-SSFP was 44±10% for left anterior descending artery, 31±7% for right coronary artery, and 30±9% for left circumflex artery. Using T2-STIR, MaR was 44±9% for left anterior descending artery, 30±8% for right coronary artery, and 30±12% for left circumflex artery. MaR was visualized in polar plots, and expected overlap was found between right coronary artery and left circumflex artery. Detailed regional data are presented for use in software algorithms as a priori information on the extent of MaR., Conclusions: For the first time, cardiovascular magnetic resonance has been used to show the main coronary perfusion territories using CE-SSFP and T2-STIR. The good agreement between CE-SSFP and T2-STIR from this study and myocardial perfusion single-photon emission computed tomography from previous studies indicates that these 3 methods depict MaR accurately in individual patients and at a group level., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01379261 and NCT01374321., (© 2016 American Heart Association, Inc.)

Background: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) using magnitude inversion recovery (IR) or phase sensitive inversion recovery (PSIR) has become clinical standard for assessment of myocardial infarction (MI). However, there is no clinical standard for quantification of MI even though multiple methods have been proposed. Simple thresholds have yielded varying results and advanced algorithms have only been validated in single center studies. Therefore, the aim of this study was to develop an automatic algorithm for MI quantification in IR and PSIR LGE images and to validate the new algorithm experimentally and compare it to expert delineations in multi-center, multi-vendor patient data., Methods: The new automatic algorithm, EWA (Expectation Maximization, weighted intensity, a priori information), was implemented using an intensity threshold by Expectation Maximization (EM) and a weighted summation to account for partial volume effects. The EWA algorithm was validated in-vivo against triphenyltetrazolium-chloride (TTC) staining (n = 7 pigs with paired IR and PSIR images) and against ex-vivo high resolution T1-weighted images (n = 23 IR and n = 13 PSIR images). The EWA algorithm was also compared to expert delineation in 124 patients from multi-center, multi-vendor clinical trials 2-6 days following first time ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) (n = 124 IR and n = 49 PSIR images)., Results: Infarct size by the EWA algorithm in vivo in pigs showed a bias to ex-vivo TTC of -1 ± 4%LVM (R = 0.84) in IR and -2 ± 3%LVM (R = 0.92) in PSIR images and a bias to ex-vivo T1-weighted images of 0 ± 4%LVM (R = 0.94) in IR and 0 ± 5%LVM (R = 0.79) in PSIR images. In multi-center patient studies, infarct size by the EWA algorithm showed a bias to expert delineation of -2 ± 6 %LVM (R = 0.81) in IR images (n = 124) and 0 ± 5%LVM (R = 0.89) in PSIR images (n = 49)., Conclusions: The EWA algorithm was validated experimentally and in patient data with a low bias in both IR and PSIR LGE images. Thus, the use of EM and a weighted intensity as in the EWA algorithm, may serve as a clinical standard for the quantification of myocardial infarction in LGE CMR images., Clinical Trial Registration: CHILL-MI: NCT01379261 ., Mitocare: NCT01374321 .

Purpose: To validate an automatic algorithm for offline T2* measurements, providing robust, vendor-independent T2*, and uncertainty estimates for iron load quantification in the heart and liver using clinically available imaging sequences., Methods: A T2* region of interest (ROI)-based algorithm was developed for robustness in an offline setting. Phantom imaging was performed on a 1.5 Tesla system, with clinically available multiecho gradient-recalled-echo (GRE) sequences for cardiac and liver imaging. A T2* single-echo GRE sequence was used as reference. Simulations were performed to assess accuracy and precision from 2000 measurements. Inter- and intraobserver variability was obtained in a patient study (n = 23)., Results: Simulations: Accuracy, in terms of the mean differences between the proposed method and true T2* ranged from 0-0.73 ms. Precision, in terms of confidence intervals of repeated measurements, was 0.06-4.74 ms showing agreement between the proposed uncertainty estimate and simulations. Phantom study: Bias and variability were 0.26 ± 4.23 ms (cardiac sequence) and -0.23 ± 1.69 ms (liver sequence). Patient study: Intraobserver variability was similar for experienced and inexperienced observers (0.03 ± 1.44 ms versus 0.16 ± 2.33 ms). Interobserver variability was 1.0 ± 3.77 ms for the heart and -0.52 ± 2.75 ms for the liver., Conclusion: The proposed algorithm was shown to provide robust T2* measurements and uncertainty estimates over the range of clinically relevant T2* values. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance., (© 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Efficacy of reperfusion therapy can be assessed as myocardial salvage index (MSI) by determining the size of myocardium at risk (MaR) and myocardial infarction (MI), (MSI = 1-MI/MaR). Cardiovascular magnetic resonance (CMR) can be used to assess MI by late gadolinium enhancement (LGE) and MaR by either T2-weighted imaging or contrast enhanced SSFP (CE-SSFP). Automatic segmentation algorithms have been developed and validated for MI by LGE as well as for MaR by T2-weighted imaging. There are, however, no algorithms available for CE-SSFP. Therefore, the aim of this study was to develop and validate automatic segmentation of MaR in CE-SSFP., Methods: The automatic algorithm applies surface coil intensity correction and classifies myocardial intensities by Expectation Maximization to define a MaR region based on a priori regional criteria, and infarct region from LGE. Automatic segmentation was validated against manual delineation by expert readers in 183 patients with reperfused acute MI from two multi-center randomized clinical trials (RCT) (CHILL-MI and MITOCARE) and against myocardial perfusion SPECT in an additional set (n = 16). Endocardial and epicardial borders were manually delineated at end-diastole and end-systole. Manual delineation of MaR was used as reference and inter-observer variability was assessed for both manual delineation and automatic segmentation of MaR in a subset of patients (n = 15). MaR was expressed as percent of left ventricular mass (%LVM) and analyzed by bias (mean ± standard deviation). Regional agreement was analyzed by Dice Similarity Coefficient (DSC) (mean ± standard deviation)., Results: MaR assessed by manual and automatic segmentation were 36 ± 10% and 37 ± 11%LVM respectively with bias 1 ± 6%LVM and regional agreement DSC 0.85 ± 0.08 (n = 183). MaR assessed by SPECT and CE-SSFP automatic segmentation were 27 ± 10%LVM and 29 ± 7%LVM respectively with bias 2 ± 7%LVM. Inter-observer variability was 0 ± 3%LVM for manual delineation and -1 ± 2%LVM for automatic segmentation., Conclusions: Automatic segmentation of MaR in CE-SSFP was validated against manual delineation in multi-center, multi-vendor studies with low bias and high regional agreement. Bias and variability was similar to inter-observer variability of manual delineation and inter-observer variability was decreased by automatic segmentation. Thus, the proposed automatic segmentation can be used to reduce subjectivity in quantification of MaR in RCT., Clinical Trial Registration: NCT01379261. NCT01374321.

The relationship between hypertrophy, perfusion abnormalities and fibrosis is unknown in young patients with hypertrophic cardiomyopathy (HCM). Since mounting evidence suggests causal relationship between myocardial ischemia and major adverse cardiac events, we sought to investigate whether (1) regional myocardial perfusion is decreased in young HCM patients and in individuals at risk of HCM, and (2) hypoperfused areas are larger than areas with fibrosis. HCM patients (n = 12), HCM-risk subjects (n = 15) and controls (n = 9) were imaged on a 1.5 T MRI scanner. Myocardial hypertrophy was assessed on cine images. Perfusion images were acquired during adenosine hyperemia and at rest. Maximum upslope ratios of perfusion (stress/rest) were used for semiquantitative analysis. Fibrosis was assessed by late gadolinium enhancement (LGE). Results are presented as median and range. Perfusion in HCM-risk subjects and in non-hypertrophied segments in HCM patients showed no difference compared to controls (P = ns). Hypertrophic segments in HCM patients without LGE showed decreased perfusion compared to segments without hypertrophy [1.5 (1.1-2.3) vs. 2.0 (1.8-2.6), P < 0.001], and hypertrophic segments with LGE showed even lower perfusion using a segmental analysis [0.9 (0.6-1.8), P < 0.05]. The extent of hypoperfused myocardium in HCM patients during adenosine exceeded the extent of fibrosis on LGE [20 (0-48) vs. 4 (0-7) % slice area, P < 0.05] and hypoperfused areas at rest (P < 0.001). Regional perfusion is decreased in hypertrophied compared to non-hypertrophied myocardium and is lowest in fibrotic myocardium in young HCM patients but does not discriminate HCM-risk subjects from controls. The stress-induced hypoperfused regions exceed regions with LGE, indicating that hypoperfusion precedes fibrosis and may be a more sensitive marker of diseased myocardium in HCM.

Background: T1 mapping is widely used today in CMR, however, it underestimates true T1 values and its measurement error is influenced by several acquisition parameters. The purpose of this study was the extraction of accurate T1 data through the utilization of comprehensive, parallel Simulations for QUAntifying RElaxation Magnetic Resonance constants (SQUAREMR) of the MOLLI pulse sequence on a large population of spins with physiologically relevant tissue relaxation constants., Methods: A CMR protocol consisting of different MOLLI schemes was performed on phantoms and healthy human volunteers. For every MOLLI experiment, the identical pulse sequence was simulated for a large range of physiological combinations of relaxation constants, resulting in a database of all possible outcomes. The unknown relaxation constants were then determined by finding the simulated signals in the database that produced the least squared difference to the measured signal intensities., Results: SQUAREMR demonstrated improvement of accuracy in phantom studies and consistent mean T1 values and consistent variance across the different MOLLI schemes in humans. This was true even for tissues with long T1s and MOLLI schemes with no pause between modified-Look-Locker experiments., Conclusions: SQUAREMR enables quantification of T1 data obtained by existing clinical pulse sequences. SQUAREMR allows for correction of quantitative CMR data that have already been acquired whereas it is expected that SQUAREMR may improve data consistency and advance quantitative MR across imaging centers, vendors and experimental configurations. While this study is focused on a MOLLI-based T1-mapping technique, it could however be extended in other types of quantitative MRI throughout the body.

Background: MRI physics simulators have been developed in the past for optimizing imaging protocols and for training purposes. However, these simulators have only addressed motion within a limited scope. The purpose of this study was the incorporation of realistic motion, such as cardiac motion, respiratory motion and flow, within MRI simulations in a high performance multi-GPU environment., Methods: Three different motion models were introduced in the Magnetic Resonance Imaging SIMULator (MRISIMUL) of this study: cardiac motion, respiratory motion and flow. Simulation of a simple Gradient Echo pulse sequence and a CINE pulse sequence on the corresponding anatomical model was performed. Myocardial tagging was also investigated. In pulse sequence design, software crushers were introduced to accommodate the long execution times in order to avoid spurious echoes formation. The displacement of the anatomical model isochromats was calculated within the Graphics Processing Unit (GPU) kernel for every timestep of the pulse sequence. Experiments that would allow simulation of custom anatomical and motion models were also performed. Last, simulations of motion with MRISIMUL on single-node and multi-node multi-GPU systems were examined., Results: Gradient Echo and CINE images of the three motion models were produced and motion-related artifacts were demonstrated. The temporal evolution of the contractility of the heart was presented through the application of myocardial tagging. Better simulation performance and image quality were presented through the introduction of software crushers without the need to further increase the computational load and GPU resources. Last, MRISIMUL demonstrated an almost linear scalable performance with the increasing number of available GPU cards, in both single-node and multi-node multi-GPU computer systems., Conclusions: MRISIMUL is the first MR physics simulator to have implemented motion with a 3D large computational load on a single computer multi-GPU configuration. The incorporation of realistic motion models, such as cardiac motion, respiratory motion and flow may benefit the design and optimization of existing or new MR pulse sequences, protocols and algorithms, which examine motion related MR applications.

In order to determine the cardioprotective efficacy of acute reperfusion therapy, assessed as myocardial salvage, in patients with acute coronary occlusion, the final myocardial infarct (MI) size needs to be related to the amount of ischemic myocardium during coronary occlusion, referred to as the myocardium at risk (MaR). There are currently several imaging approaches available for quantification of both MI size and MaR in vivo of which some have been validated both in pre-clinical and clinical settings. These methods often involve the use of either myocardial perfusion SPECT or cardiac magnetic resonance (CMR). These imaging methods could potentially be used to further develop and validate ECG methods for determination of MI size and MaR. Therefore, the aim of the present review is to give an overview of myocardial perfusion SPECT and CMR methods available for assessment of myocardial salvage by determination of MI size and MaR., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A new step-by-step comprehensive MR physics simulator (MRISIMUL) of the Bloch equations is presented. The aim was to develop a magnetic resonance imaging (MRI) simulator that makes no assumptions with respect to the underlying pulse sequence and also allows for complex large-scale analysis on a single computer without requiring simplifications of the MRI model. We hypothesized that such a simulation platform could be developed with parallel acceleration of the executable core within the graphic processing unit (GPU) environment. MRISIMUL integrates realistic aspects of the MRI experiment from signal generation to image formation and solves the entire complex problem for densely spaced isochromats and for a densely spaced time axis. The simulation platform was developed in MATLAB whereas the computationally demanding core services were developed in CUDA-C. The MRISIMUL simulator imaged three different computer models: a user-defined phantom, a human brain model and a human heart model. The high computational power of GPU-based simulations was compared against other computer configurations. A speedup of about 228 times was achieved when compared to serially executed C-code on the CPU whereas a speedup between 31 to 115 times was achieved when compared to the OpenMP parallel executed C-code on the CPU, depending on the number of threads used in multithreading (2-8 threads). The high performance of MRISIMUL allows its application in large-scale analysis and can bring the computational power of a supercomputer or a large computer cluster to a single GPU personal computer.

Objectives: This study's primary objective was to determine the sensitivity, specificity, and accuracy of fully quantitative stress perfusion cardiac magnetic resonance (CMR) versus a reference standard of quantitative coronary angiography. We hypothesized that fully quantitative analysis of stress perfusion CMR would have high diagnostic accuracy for identifying significant coronary artery stenosis and exceed the accuracy of semiquantitative measures of perfusion and qualitative interpretation., Background: Relatively few studies apply fully quantitative CMR perfusion measures to patients with coronary disease and comparisons to semiquantitative and qualitative methods are limited., Methods: Dual bolus dipyridamole stress perfusion CMR exams were performed in 67 patients with clinical indications for assessment of myocardial ischemia. Stress perfusion images alone were analyzed with a fully quantitative perfusion (QP) method and 3 semiquantitative methods including contrast enhancement ratio, upslope index, and upslope integral. Comprehensive exams (cine imaging, stress/rest perfusion, late gadolinium enhancement) were analyzed qualitatively with 2 methods including the Duke algorithm and standard clinical interpretation. A 70% or greater stenosis by quantitative coronary angiography was considered abnormal., Results: The optimum diagnostic threshold for QP determined by receiver-operating characteristic curve occurred when endocardial flow decreased to <50% of mean epicardial flow, which yielded a sensitivity of 87% and specificity of 93%. The area under the curve for QP was 92%, which was superior to semiquantitative methods: contrast enhancement ratio: 78%; upslope index: 82%; and upslope integral: 75% (p = 0.011, p = 0.019, p = 0.004 vs. QP, respectively). Area under the curve for QP was also superior to qualitative methods: Duke algorithm: 70%; and clinical interpretation: 78% (p < 0.001 and p < 0.001 vs. QP, respectively)., Conclusions: Fully quantitative stress perfusion CMR has high diagnostic accuracy for detecting obstructive coronary artery disease. QP outperforms semiquantitative measures of perfusion and qualitative methods that incorporate a combination of cine, perfusion, and late gadolinium enhancement imaging. These findings suggest a potential clinical role for quantitative stress perfusion CMR., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Prior work has demonstrated that magnetic resonance imaging (MRI) strain can separate necrotic/stunned myocardium from healthy myocardium in the left ventricle (LV). We surmised that high-resolution MRI strain, using navigator-echo-triggered DENSE, could differentiate radiofrequency ablated tissue around the pulmonary vein (PV) from tissue that had not been damaged by radiofrequency energy, similarly to navigated 3D myocardial delayed enhancement (3D-MDE)., Methods and Results: A respiratory-navigated 2D-DENSE sequence was developed, providing strain encoding in two spatial directions with 1.2 × 1.0 × 4 mm(3) resolution. It was tested in the LV of infarcted sheep. In four swine, incomplete circumferential lesions were created around the right superior pulmonary vein (RSPV) using ablation catheters, recorded with electro-anatomic mapping, and imaged 1 h later using atrial-diastolic DENSE and 3D-MDE at the left atrium/RSPV junction. DENSE detected ablation gaps (regions with >12% strain) in similar positions to 3D-MDE (2D cross-correlation 0.89 ± 0.05). Low-strain (<8%) areas were, on average, 33% larger than equivalent MDE regions, so they include both injured and necrotic regions. Optimal DENSE orientation was perpendicular to the PV trunk, with high shear strain in adjacent viable tissue appearing as a sensitive marker of ablation lesions., Conclusions: Magnetic resonance imaging strain may be a non-contrast alternative to 3D-MDE in intra-procedural monitoring of atrial ablation lesions.

Context: Unrecognized myocardial infarction (MI) is prognostically important. Electrocardiography (ECG) has limited sensitivity for detecting unrecognized MI (UMI)., Objective: Determine prevalence and mortality risk for UMI detected by cardiac magnetic resonance (CMR) imaging or ECG among older individuals., Design, Setting, and Participants: ICELAND MI is a cohort substudy of the Age, Gene/Environment Susceptibility-Reykjavik Study (enrollment January 2004-January 2007) using ECG or CMR to detect UMI. From a community-dwelling cohort of older individuals in Iceland, data for 936 participants aged 67 to 93 years were analyzed, including 670 who were randomly selected and 266 with diabetes., Main Outcome Measures: Prevalence and mortality of MI through September 1, 2011. Results reported with 95% confidence limits and net reclassification improvement (NRI)., Results: Of 936 participants, 91 had recognized MI (RMI) (9.7%; 95% CI, 8% to 12%), and 157 had UMI detected by CMR (17%; 95% CI, 14% to 19%), which was more prevalent than the 46 UMI detected by ECG (5%; 95% CI, 4% to 6%; P < .001). Participants with diabetes (n = 337) had more UMI detected by CMR than by ECG (n = 72; 21%; 95% CI, 17% to 26%, vs n = 15; 4%; 95% CI, 2% to 7%; P < .001). Unrecognized MI by CMR was associated with atherosclerosis risk factors, coronary calcium, coronary revascularization, and peripheral vascular disease. Over a median of 6.4 years, 30 of 91 participants (33%; 95% CI, 23% to 43%) with RMI died, and 44 of 157 participants (28%; 95% CI, 21% to 35%) with UMI died, both higher rates than the 119 of 688 participants (17%; 95% CI, 15% to 20%) with no MI who died. Unrecognized MI by CMR improved risk stratification for mortality over RMI (NRI, 0.34; 95% CI, 0.16 to 0.53). Adjusting for age, sex, diabetes, and RMI, UMI by CMR remained associated with mortality (hazard ratio [HR], 1.45; 95% CI, 1.02 to 2.06, absolute risk increase [ARI], 8%) and significantly improved risk stratification for mortality (NRI, 0.16; 95% CI, 0.01 to 0.31), but UMI by ECG did not (HR, 0.88; 95% CI, 0.45 to 1.73; ARI, -2%; NRI, -0.05; 95% CI, -0.17 to 0.05). Compared with those with RMI, participants with UMI by CMR used cardiac medications such as statins less often (36%; 95% CI, 28% to 43%, or 56/157, vs 73%; 95% CI, 63% to 82%, or 66/91; P < .001)., Conclusions: In a community-based cohort of older individuals, the prevalence of UMI by CMR was higher than the prevalence of RMI and was associated with increased mortality risk. In contrast, UMI by ECG prevalence was lower than that of RMI and was not associated with increased mortality risk., Trial Registration: clinicaltrials.gov Identifier: NCT01322568.

Objectives: The aim of this study was to determine whether cardiac magnetic resonance (CMR) in vivo T1 mapping can measure myocardial area at risk (AAR) compared with microspheres or T2 mapping CMR., Background: If T2-weighted CMR is abnormal in the AAR due to edema related to myocardial ischemia, then T1-weighted CMR should also be able to detect and accurately quantify AAR., Methods: Dogs (n = 9) underwent a 2-h coronary occlusion followed by 4 h of reperfusion. CMR of the left ventricle was performed for mapping of T1 and T2 prior to any contrast administration. AAR was defined as regions that had a T1 or T2 value (ms) >2 SD from remote myocardium, and regions with microsphere blood flow (ml/min/g) during occlusion <2 SD from remote myocardium. Infarct size was determined by triphenyltetrazolium chloride staining., Results: The relaxation parameters T1 and T2 were increased in the AAR compared with remote myocardium (mean ± SD: T1, 1,133 ± 55 ms vs. 915 ± 33 ms; T2, 71 ± 6 ms vs. 49 ± 3 ms). On a slice-by-slice basis (n = 78 slices), AAR by T1 and T2 mapping correlated (R(2) = 0.95, p < 0.001) with good agreement (mean ± 2 SD: 0.4 ± 16.6% of slice). On a whole-heart analysis, T1 measurements of left ventricular mass, AAR, and myocardial salvage correlated to microsphere measures (R(2) = 0.94) with good agreement (mean ± 2 SD: -1.4 ± 11.2 g of myocardium). Corresponding T2 measurements of left ventricular mass, AAR, and salvage correlated to microsphere analysis (R(2) = 0.96; mean ± 2 SD: agreement 1.6 ± 9.2 g of myocardium). This yielded a median infarct size of 30% of the AAR (range 12% to 52% of AAR)., Conclusions: For determining AAR after acute myocardial infarction, noncontrast T1 mapping and T2 mapping sequences yield similar quantitative results, and both agree well with microspheres. The relaxation properties T1 and T2 both change in a way that is consistent with the presence of myocardial edema following myocardial ischemia/reperfusion., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)