Characterization of quantitative susceptibility mapping in the left ventricular myocardium.

BACKGROUND: Myocardial quantitative susceptibility mapping (QSM) may offer better specificity to iron than conventional T2* imaging in the assessment of cardiac diseases, including intra-myocardial hemorrhage. However, the precision and repeatability of cardiac QSM have not yet been characterized. The aim of this study is to characterize these key metrics in a healthy volunteer cohort and show the feasibility of the method in patients. METHODS: Free breathing respiratory-navigated multi-echo 3D gradient echo images were acquired, from which QSM maps were reconstructed using the Morphology Enhanced Dipole Inversion toolbox. This technique was first evaluated in a susceptibility phantom containing tubes with known concentrations of gadolinium. In vivo characterization of myocardial QSM was then performed in a cohort of 10 healthy volunteers where each subject was scanned twice. Mean segment susceptibility, precision (standard deviation of voxel magnetic susceptibilities within one segment), and repeatability (absolute difference in segment mean susceptibility between repeats) of QSM were calculated for each American Heart Association (AHA) myocardial segment. Finally, the feasibility of the method was shown in 10 patients, including four with hemorrhagic infarcts. RESULTS: The phantom experiment showed a strong linear relationship between measured and predicted susceptibility shifts (R2 > 0.99). For the healthy volunteer cohort, AHA segment analysis showed the mean segment susceptibility was 0.00 ± 0.02 ppm, the mean precision was 0.05 ± 0.04 ppm, and the mean repeatability was 0.02 ± 0.02 ppm. Cardiac QSM was successfully performed in all patients. Focal iron deposits were successfully visualized in the patients with hemorrhagic myocardial infarctions. CONCLUSION: The precision and repeatability of cardiac QSM were successfully characterized in phantom and in vivo experiments. The feasibility of the technique was also successfully demonstrated in patients. While challenges still remain, further clinical evaluation of the technique is now warranted. TRIAL REGISTRATION: This work does not report on a health care intervention.

Mitral Annulus Disjunction in consecutive patients undergoing Cardiac Magnetic Resonance: where is the boundary between normality and disease?

BACKGROUND: The presence of mitral annulus disjunction (MAD) has been considered a high-risk feature for sudden cardiac death based on selected study populations. We aimed to assess the prevalence of MAD in consecutive patients undergoing clinically-indicated Cardiac Magnetic Resonance (CMR), its association with ventricular arrhythmias, Mitral Valve Prolapse (MVP), and other CMR features. METHODS: This single-center retrospective study included consecutive patients referred to CMR at our Institution between June 2021 and November 2021. The MAD was defined as a ≥1mm displacement between the left atrial wall-mitral valve leaflet junction and the left ventricular wall during end-systole. The MAD extent was defined as the maximum longitudinal displacement. Associates of MAD were evaluated at uni- and multi-variariable regression analysis. A study endpoint including (aborted) sudden cardiac death, unexplained syncope, and sustained ventricular tachycardia was evaluated at 12-month follow-up. RESULTS: Four-hundred-forty-one patients (55±18 years, 61% males) were included, and 29 (7%) had MVP. The prevalence of MAD ≥1mm, 4mm, and 6mm were 214 (49%), 63 (14%), and 15 (3%), respectively. Patients with MVP showed a higher prevalence of MAD greater than 1mm (90% vs. 46%; p<0.001), 4mm (48% vs. 12%; p<0.001), and 6mm (10% vs. 3%; p=0.03), and a greater MAD extent (4.2mm, 3.0-5.7mm vs. 2.8mm, 1.9-4.0mm; p<0.001) than patients without MVP. The MVP was the only morpho-functional abnormality associated with MAD at multivariable analysis (p<0.001). A high burden of ventricular ectopic beats at baseline Holter-ECG was associated with MAD ≥4mm and MAD extent (p<0.05). The presence of MAD ≥1mm (0.9% vs. 1.8%; p=0.46), MAD ≥4mm (1.6% vs. 1.3%; p=0.87), or MVP (3.5% vs. 1.2%; p=0.32) were not associated with the study endpoint, whereas patients with MAD ≥6mm showed a trend towards a higher likelihood of the study endpoint (6.7% vs. 1.2%; p=0.07). CONCLUSIONS: A MAD of limited entity was common in consecutive patients undergoing CMR. Patients with MVP showed higher prevalence and greater extent of MAD. Extended MAD was rarer and showed association with ventricular arrhythmias at baseline. The mid-term prognosis of MAD seems benign, however prospective studies are warranted to search for potential "malignant MAD extents" to improve patients' risk stratification.

Myocardial Fibrosis at Cardiac MRI Helps Predict Adverse Clinical Outcome in Patients with Mitral Valve Prolapse.

Background Patients with mitral valve prolapse (MVP) may develop adverse outcomes even in the absence of mitral regurgitation or left ventricular (LV) dysfunction. Purpose To investigate the prognostic value of mitral annulus disjunction (MAD) and myocardial fibrosis at late gadolinium enhancement (LGE) cardiac MRI in patients with MVP without moderate-to-severe mitral regurgitation or LV dysfunction. Materials and Methods In this longitudinal retrospective study, 118 144 cardiac MRI studies were evaluated between October 2007 and June 2020 at 15 European tertiary medical centers. Follow-up was from the date of cardiac MRI examination to June 2020; the minimum and maximum follow-up intervals were 6 months and 156 months, respectively. Patients were excluded if at least one of the following conditions was present: cardiomyopathy, LV ejection fraction less than 40%, ischemic heart disease, congenital heart disease, inflammatory heart disease, moderate or worse mitral regurgitation, participation in competitive sport, or electrocardiogram suggestive of channelopathies. In the remainder, cardiac MRI studies were reanalyzed, and patients were included if they were aged 18 years or older, MVP was diagnosed at cardiac MRI, and clinical information and electrocardiogram monitoring were available within 3 months from cardiac MRI examination. The end point was a composite of adverse outcomes: sustained ventricular tachycardia (VT), sudden cardiac death (SCD), or unexplained syncope. Multivariable Cox regression analysis was performed. Results A total of 474 patients (mean age, 47 years ± 16 [SD]; 244 women) were included. Over a median follow-up of 3.3 years, 18 patients (4%) reached the study end point. LGE presence (hazard ratio, 4.2 [95% CI: 1.5, 11.9]; P = .006) and extent (hazard ratio, 1.2 per 1% increase [95% CI: 1.1, 1.4]; P = .006), but not MAD presence (P = .89), were associated with clinical outcome. LGE presence had incremental prognostic value over MVP severity and sustained VT and aborted SCD at baseline (area under the receiver operating characteristic curve, 0.70 vs 0.62; P = .03). Conclusion In contrast to mitral annulus disjunction, myocardial fibrosis determined according to late gadolinium enhancement at cardiac MRI was associated with adverse outcome in patients with mitral valve prolapse without moderate-to-severe mitral regurgitation or left ventricular dysfunction. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gerber in this issue.

AI Cardiac MRI Scar Analysis Aids Prediction of Major Arrhythmic Events in the Multicenter DERIVATE Registry.

Background Scar burden with late gadolinium enhancement (LGE) cardiac MRI (CMR) predicts arrhythmic events in patients with postinfarction in single-center studies. However, LGE analysis requires experienced human observers, is time consuming, and introduces variability. Purpose To test whether postinfarct scar with LGE CMR can be quantified fully automatically by machines and to compare the ability of LGE CMR scar analyzed by humans and machines to predict arrhythmic events. Materials and Methods This study is a retrospective analysis of the multicenter, multivendor CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry. Patients with chronic heart failure, echocardiographic left ventricular ejection fraction (LVEF) of less than 50%, and LGE CMR were recruited (from January 2015 through December 2020). In the current study, only patients with ischemic cardiomyopathy were included. Quantification of total, dense, and nondense scars was carried out by two experienced readers or a Ternaus network, trained and tested with LGE images of 515 and 246 patients, respectively. Univariable and multivariable Cox analyses were used to assess patient and cardiac characteristics associated with a major adverse cardiac event (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare model performances. Results In 761 patients (mean age, 65 years ± 11, 671 men), 83 MACEs occurred. With use of the testing group, univariable Cox-analysis found New York Heart Association class, left ventricle volume and/or function parameters (by echocardiography or CMR), guideline criterion (LVEF of ≤35% and New York Heart Association class II or III), and LGE scar analyzed by humans or the machine-learning algorithm as predictors of MACE. Machine-based dense or total scar conferred incremental value over the guideline criterion for the association with MACE (AUC: 0.68 vs 0.63, P = .02 and AUC: 0.67 vs 0.63, P = .01, respectively). Modeling with competing risks yielded for dense and total scar (AUC: 0.67 vs 0.61, P = .01 and AUC: 0.66 vs 0.61, P = .005, respectively). Conclusion In this analysis of the multicenter CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry, fully automatic machine learning-based late gadolinium enhancement analysis reliably quantifies myocardial scar mass and improves the current prediction model that uses guideline-based risk criteria for implantable cardioverter defibrillator implantation. ClinicalTrials.gov registration no.: NCT03352648 Published under a CC BY 4.0 license. Supplemental material is available for this article.

Effectiveness of the risk stratification proposed by the 2022 European Heart Rhythm Association Expert Consensus statement on arrhythmic mitral valve prolapse.

BACKGROUND: Recently, an expert consensus statement proposed indications where implantation of a primary prevention implantable cardioverter-defibrillator (ICD) may be reasonable in patients with mitral valve prolapse (MVP). The objective was to evaluate the proposed risk stratification by the expert consensus statement. METHODS: Consecutive patients with MVP without alternative arrhythmic substrates with cardiac magnetic resonance imaging (CMR) were included in a single-center retrospective registry. Arrhythmic MVP (AMVP) was defined as a total premature ventricular complex burden ≥5%, non-sustained ventricular tachycardia (VT), VT, or ventricular fibrillation. The end point was a composite of SCD, VT, inducible VT, and appropriate ICD shocks. RESULTS: In total, 169 patients (52.1% male, median age 51.4 years) were included and 99 (58.6%) were classified as AMVP. Multivariate logistic regression identified the presence of late gadolinium enhancement (OR 2.82, 95%CI 1.45-5.50) and mitral annular disjunction (OR 1.98, 95%CI 1.02-3.86) as only predictors of AMVP. According to the EHRA risk stratification, 5 patients with AMVP (5.1%) had a secondary prevention ICD indication, while in 69 patients (69.7%) the implantation of an ICD may be reasonable. During a median follow-up of 8.0 years (IQR 5.0-15.6), the incidence rate for the composite arrhythmic end point was 0.3%/year (95%CI 0.1-0.8). CONCLUSION: More than half of MVP patients referred for CMR met the AMVP diagnostic criteria. Despite low long-term event rates, in 70% of patients with AMVP the implantation of an ICD may be reasonable. Risk stratification of SCD in MVP remains an important knowledge gap and requires urgent investigation.

Quantification of balanced SSFP myocardial perfusion imaging at 1.5 T: Impact of the reference image.

PURPOSE: To investigate the use of a high flip-angle (HFA) balanced SSFP (bSSFP) reference image (in comparison to conventional proton density [PD]-weighted reference images) for conversion of bSSFP myocardial perfusion images into dynamic T1 maps for improved myocardial blood flow (MBF) quantification at 1.5 T. METHODS: The HFA-bSSFP (flip angle [FA] = 50°), PD gradient-echo (PD-GRE; FA = 5°), and PD-bSSFP (FA = 8°) reference images were acquired before a dual-sequence bSSFP perfusion acquisition. Simulations were used to study accuracy and precision of T1 and MBF quantification using the three techniques. The accuracy and precision of T1 , and the precision and intersegment variability of MBF were compared among the three techniques in 8 patients under rest conditions. RESULTS: In simulations, HFA-bSSFP demonstrated improved T1 /MBF precision (higher T1 /MBF SD of 30%-80%/50%-100% and 30%-90%/60%-115% for PD-GRE and PD-bSSFP, respectively). Proton density-GRE and PD-bSSFP were more sensitive to effective FA than HFA-bSSFP (maximum T1 /MBF errors of 13%/43%, 20%/43%, and 1%/3%, respectively). Sensitivity of all techniques (defined as T1 /MBF errors) to native T1 , native T2 , and effective saturation efficiency were negligible (<1%/<1%), moderate (<14%/<19%), and high (<63%/<94%), respectively. In vivo, no difference in T1 accuracy was observed among HFA-bSSFP, PD-GRE, and PD-bSSFP (-9 ± 44 ms vs -28 ± 55 ms vs -22 ± 71 ms, respectively; p > .08). The HFA-bSSFP led to improved T1 /MBF precision (T1 /MBF SD: 41 ± 19 ms/0.24 ± 0.08 mL/g/min vs PD-GRE: 48 ± 20 ms/0.29 ± 0.09 mL/g/min and PD-bSSFP: 59 ± 23 ms/0.33 ± 0.11 mL/g/min; p ≤ .02) and lower MBF intersegment variability (0.14 ± 0.09 mL/g/min vs PD-GRE: 0.21 ± 0.09 mL/g/min and PD-bSSFP: 0.20 ± 0.10 mL/g/min; p ≤ .046). CONCLUSION: We have demonstrated the feasibility of using a HFA-bSSFP reference image for MBF quantification of bSSFP perfusion imaging at 1.5 T. Results from simulations demonstrate that the HFA-bSSFP reference image results in improved precision and reduced sensitivity to effective FA compared with conventional techniques using a PD reference image. Preliminary in vivo data acquired at rest also demonstrate improved precision and intersegment variability using the HFA-bSSFP technique compared with PD techniques; however, a clinical study in patients with coronary artery disease under stress conditions is required to determine the clinical significance of this finding.

Simultaneous multislice steady-state free precession myocardial perfusion with full left ventricular coverage and high resolution at 1.5 T.

PURPOSE: To implement and evaluate a simultaneous multi-slice balanced SSFP (SMS-bSSFP) perfusion sequence and compressed sensing reconstruction for cardiac MR perfusion imaging with full left ventricular (LV) coverage (nine slices/heartbeat) and high spatial resolution (1.4 × 1.4 mm2 ) at 1.5T. METHODS: A preliminary study was performed to evaluate the performance of blipped controlled aliasing in parallel imaging (CAIPI) and RF-CAIPI with gradient-controlled local Larmor adjustment (GC-LOLA) in the presence of fat. A nine-slice SMS-bSSFP sequence using RF-CAIPI with GC-LOLA with high spatial resolution (1.4 × 1.4 mm2 ) and a conventional three-slice sequence with conventional spatial resolution (1.9 × 1.9 mm2 ) were then acquired in 10 patients under rest conditions. Qualitative assessment was performed to assess image quality and perceived signal-to-noise ratio (SNR) on a 4-point scale (0: poor image quality/low SNR; 3: excellent image quality/high SNR), and the number of myocardial segments with diagnostic image quality was recorded. Quantitative measurements of myocardial sharpness and upslope index were performed. RESULTS: Fat signal leakage was significantly higher for blipped CAIPI than for RF-CAIPI with GC-LOLA (7.9% vs. 1.2%, p = 0.010). All 10 SMS-bSSFP perfusion datasets resulted in 16/16 diagnostic myocardial segments. There were no significant differences between the SMS and conventional acquisitions in terms of image quality (2.6 ± 0.6 vs. 2.7 ± 0.2, p = 0.8) or perceived SNR (2.8 ± 0.3 vs. 2.7 ± 0.3, p = 0.3). Inter-reader variability was good for both image quality (ICC = 0.84) and perceived SNR (ICC = 0.70). Myocardial sharpness was improved using the SMS sequence compared to the conventional sequence (0.37 ± 0.08 vs 0.32 ± 0.05, p < 0.001). There was no significant difference between measurements of upslope index for the SMS and conventional sequences (0.11 ± 0.04 vs. 0.11 ± 0.03, p = 0.84). CONCLUSION: SMS-bSSFP with multiband factor 3 and compressed sensing reconstruction enables cardiac MR perfusion imaging with three-fold increased spatial coverage and improved myocardial sharpness compared to a conventional sequence, without compromising perceived SNR, image quality, upslope index or number of diagnostic segments.

Is heart failure with preserved ejection fraction a 'dementia' of the heart?

Heart failure with preserved ejection fraction (HFpEF) remains an elusive entity, due to its heterogeneous clinical profile and an arbitrarily defined nosology. Several pathophysiological mechanisms recognized as central for the development of HFpEF appear to be in common with the process of physiological aging of the heart. Both conditions are characterized by progressive impairment in cardiac function, accompanied by left ventricular hypertrophy, diastolic dysfunction, sarcomeric, and metabolic abnormalities. The neurological paradigm of dementia-intended as a progressive, multifactorial organ damage with decline of functional reserve, eventually leading to irreversible dysfunction-is well suited to represent HFpEF. In such perspective, certain phenotypes of HFpEF may be viewed as a maladaptive response to environmental modifiers, causing premature and pathological aging of the heart. We here propose that the 'HFpEF syndrome' may reflect the interplay of adverse structural remodelling and erosion of functional reserve, mirroring the processes leading to dementia in the brain. The resulting conceptual framework may help advance our understanding of HFpEF and unravel potential therapeutical targets.

Efficient non-contrast enhanced 3D Cartesian cardiovascular magnetic resonance angiography of the thoracic aorta in 3 min.

BACKGROUND: The application of cardiovascular magnetic resonance angiography (CMRA) for the assessment of thoracic aortic disease is often associated with prolonged and unpredictable acquisition times and residual motion artefacts. To overcome these limitations, we have integrated undersampled acquisition with image-based navigators and inline non-rigid motion correction to enable a free-breathing, contrast-free Cartesian CMRA framework for the visualization of the thoracic aorta in a short and predictable scan of 3 min. METHODS: 35 patients with thoracic aortic disease (36 ± 13y, 14 female) were prospectively enrolled in this single-center study. The proposed 3D T2-prepared balanced steady state free precession (bSSFP) sequence with image-based navigator (iNAV) was compared to the clinical 3D T2-prepared bSSFP with diaphragmatic-navigator gating (dNAV), in terms of image acquisition time. Three cardiologists blinded to iNAV vs. dNAV acquisition, recorded image quality scores across four aortic segments and their overall diagnostic confidence. Contrast ratio (CR) and relative standard deviation (RSD) of signal intensity (SI) in the corresponding segments were estimated. Co-axial aortic dimensions in six landmarks were measured by two readers to evaluate the agreement between the two methods, along with inter-observer and intra-observer agreement. Kolmogorov-Smirnov test, Mann-Whitney U (MWU), Bland-Altman analysis (BAA), intraclass correlation coefficient (ICC) were used for statistical analysis. RESULTS: The scan time for the iNAV-based approach was significantly shorter (3.1 ± 0.5 min vs. 12.0 ± 3.0 min for dNAV, P = 0.005). Reconstruction was performed inline in 3.0 ± 0.3 min. Diagnostic confidence was similar for the proposed iNAV versus dNAV for all three reviewers (Reviewer 1: 3.9 ± 0.3 vs. 3.8 ± 0.4, P = 0.7; Reviewer 2: 4.0 ± 0.2 vs. 3.9 ± 0.3, P = 0.4; Reviewer 3: 3.8 ± 0.4 vs. 3.7 ± 0.6, P = 0.3). The proposed method yielded higher image quality scores in terms of artefacts from respiratory motion, and non-diagnostic images due to signal inhomogeneity were observed less frequently. While the dNAV approach outperformed the iNAV method in the CR assessment, the iNAV sequence showed improved signal homogeneity along the entire thoracic aorta [RSD SI 5.1 (4.4, 6.5) vs. 6.5 (4.6, 8.6), P = 0.002]. BAA showed a mean difference of < 0.05 cm across the 6 landmarks between the two datasets. ICC showed excellent inter- and intra-observer reproducibility. CONCLUSIONS: Thoracic aortic iNAV-based CMRA with fast acquisition (~ 3 min) and inline reconstruction (3 min) is proposed, resulting in high diagnostic confidence and reproducible aortic measurements.

Quantitative susceptibility mapping (QSM) of the cardiovascular system: challenges and perspectives.

Quantitative susceptibility mapping (QSM) is a powerful, non-invasive, magnetic resonance imaging (MRI) technique that relies on measurement of magnetic susceptibility. So far, QSM has been employed mostly to study neurological disorders characterized by iron accumulation, such as Parkinson's and Alzheimer's diseases. Nonetheless, QSM allows mapping key indicators of cardiac disease such as blood oxygenation and myocardial iron content. For this reason, the application of QSM offers an unprecedented opportunity to gain a better understanding of the pathophysiological changes associated with cardiovascular disease and to monitor their evolution and response to treatment. Recent studies on cardiovascular QSM have shown the feasibility of a non-invasive assessment of blood oxygenation, myocardial iron content and myocardial fibre orientation, as well as carotid plaque composition. Significant technical challenges remain, the most evident of which are related to cardiac and respiratory motion, blood flow, chemical shift effects and susceptibility artefacts. Significant work is ongoing to overcome these challenges and integrate the QSM technique into clinical practice in the cardiovascular field.

High-resolution non-contrast free-breathing coronary cardiovascular magnetic resonance angiography for detection of coronary artery disease: validation against invasive coronary angiography.

BACKGROUND: Coronary artery disease (CAD) is the single most common cause of death worldwide. Recent technological developments with coronary cardiovascular magnetic resonance angiography (CCMRA) allow high-resolution free-breathing imaging of the coronary arteries at submillimeter resolution without contrast in a predictable scan time of ~ 10 min. The objective of this study was to determine the diagnostic accuracy of high-resolution CCMRA for CAD detection against the gold standard of invasive coronary angiography (ICA). METHODS: Forty-five patients (15 female, 62 ± 10 years) with suspected CAD underwent sub-millimeter-resolution (0.6 mm3) non-contrast CCMRA at 1.5T in this prospective clinical study from 2019-2020. Prior to CCMR, patients were given an intravenous beta blockers to optimize heart rate control and sublingual glyceryl trinitrate to promote coronary vasodilation. Obstructive CAD was defined by lesions with ≥ 50% stenosis by quantitative coronary angiography on ICA. RESULTS: The mean duration of image acquisition was 10.4 ± 2.1 min. On a per patient analysis, the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 95% (75-100), 54% (36-71), 60% (42-75) and 93% (70-100), respectively. On a per vessel analysis the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 80% (63-91), 83% (77-88), 49% (36-63) and 95% (90-98), respectively. CONCLUSION: As an important step towards clinical translation, we demonstrated a good diagnostic accuracy for CAD detection using high-resolution CCMRA, with high sensitivity and negative predictive value. The positive predictive value is moderate, and combination with CMR stress perfusion may improve the diagnostic accuracy. Future multicenter evaluation is now required.

Fully self-gated free-running 3D Cartesian cardiac CINE with isotropic whole-heart coverage in less than 2 min.

PURPOSE: To develop a novel fast water-selective free-breathing 3D Cartesian cardiac CINE scan with full self-navigation and isotropic whole-heart (WH) coverage. METHODS: A free-breathing 3D Cartesian cardiac CINE scan with a water-selective balanced steady-state free precession and a continuous (non-ECG-gated) variable-density Cartesian sampling with spiral profile ordering, out-inward sampling and acquisition-adaptive alternating tiny golden and golden angle increment between spiral arms is proposed. Data is retrospectively binned based on respiratory and cardiac self-navigation signals. A translational respiratory-motion-corrected and cardiac-motion-resolved image is reconstructed with a multi-bin patch-based low-rank reconstruction (MB-PROST) within about 15 min. A respiratory-motion-resolved approach is also investigated. The proposed 3D Cartesian cardiac CINE is acquired in sagittal orientation in 1 min 50 s for 1.9 mm3 isotropic WH coverage. Left ventricular (LV) function parameters and image quality derived from a blinded reading of the proposed 3D CINE framework are compared against conventional multi-slice 2D CINE imaging in 10 healthy subjects and 10 patients with suspected cardiovascular disease. RESULTS: The proposed framework provides free-breathing 3D cardiac CINE images with 1.9 mm3 spatial and about 45 ms temporal resolution in a short acquisition time (<2 min). LV function parameters derived from 3D CINE were in good agreement with 2D CINE (10 healthy subjects and 10 patients). Bias and confidence intervals were obtained for end-systolic volume, end-diastolic volume and ejection fraction of 0.1 ± 3.5 mL, -0.6 ± 8.2 mL and -0.1 ± 2.2%, respectively. CONCLUSION: The proposed framework enables isotropic 3D Cartesian cardiac CINE under free breathing for fast assessment of cardiac anatomy and function.

T1, T2, and Fat Fraction Cardiac MR Fingerprinting: Preliminary Clinical Evaluation.

BACKGROUND: Dixon cardiac magnetic resonance fingerprinting (MRF) has been recently introduced to simultaneously provide water T1 , water T2 , and fat fraction (FF) maps. PURPOSE: To assess Dixon cardiac MRF repeatability in healthy subjects and its clinical feasibility in a cohort of patients with cardiovascular disease. POPULATION: T1MES phantom, water-fat phantom, 11 healthy subjects and 19 patients with suspected cardiovascular disease. STUDY TYPE: Prospective. FIELD STRENGTH/SEQUENCE: 1.5T, inversion recovery spin echo (IRSE), multiecho spin echo (MESE), modified Look-Locker inversion recovery (MOLLI), T2 gradient spin echo (T2 -GRASE), 6-echo gradient rewound echo (GRE), and Dixon cardiac MRF. ASSESSMENT: Dixon cardiac MRF precision was assessed through repeated scans against conventional MOLLI, T2 -GRASE, and PDFF in phantom and 11 healthy subjects. Dixon cardiac MRF native T1 , T2 , FF, postcontrast T1 and synthetic extracellular volume (ECV) maps were assessed in 19 patients in comparison to conventional sequences. Measurements in patients were performed in the septum and in late gadolinium enhanced (LGE) areas and assessed using mean value distributions, correlation, and Bland-Altman plots. Image quality and diagnostic confidence were assessed by three experts using 5-point scoring scales. STATISTICAL TESTS: Paired Wilcoxon rank signed test and paired t-tests were applied. Statistical significance was indicated by *(P < 0.05). RESULTS: Dixon cardiac MRF showed good overall precision in phantom and in vivo. Septal average repeatability was ~23 msec for T1 , ~2.2 msec for T2 , and ~1% for FF. Biases in healthy subjects/patients were measured at +37 msec*/+60 msec* and -8.8 msec*/-8 msec* when compared to MOLLI and T2 -GRASE, respectively. No statistically significant differences in postcontrast T1 (P = 0.17) and synthetic ECV (P = 0.19) measurements were observed in patients. DATA CONCLUSION: Dixon cardiac MRF attained good overall precision in phantom and healthy subjects, while providing coregistered T1 , T2 , and fat fraction maps in a single breath-hold scan with similar or better image quality than conventional methods in patients. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

Head-to-head comparison of multiple cardiovascular magnetic resonance techniques for the detection and quantification of intramyocardial haemorrhage in patients with ST-elevation myocardial infarction.

OBJECTIVES: T2*-weighted (T2*w) is deemed as a reference standard for post-infarction intramyocardial haemorrhage (IMH). However, high proportion of T2* images is affected by off-resonance artefacts hampering image interpretation. Diagnostic accuracy and precision of alternative techniques for IMH diagnosis and quantification have been seldomly investigated. METHODS AND RESULTS: Between April 2016 and May 2017, 50 ST-segment elevation myocardial infarction patients (66% male, 57 ± 17 years) and 15 healthy controls (60% male, 58 ± 13) were consecutively enrolled. Subjects underwent head-to-head comparison of single mid-infarct slice acquired on black-blood T2-weighted short-TI-inversion recovery (T2w-STIR), bright-blood T2prep-steady-state-free precession (T2prep-SSFP), and T2/T1 maps for IMH diagnosis and quantification against T2*w. All images were graded for quality (grade 1: very poor; grade 4: excellent) and diagnostic confidence (Likert scale, 1: very unsure and 5: highly confident). Reduced relaxation time/hypointense region (hypocore) embedded in infarct-related oedema on T2 map, T1 map, and T2w-STIR had the best overall diagnostic accuracy (per-subject: 91%, 86%, and 86%, respectively; per segment: 95%, 93%, and 93%, respectively). By mixed-effects analysis, image quality, and diagnostic confidence were higher for T2 map and T1 maps than T2*w (p < 0.05 for both scores). For IMH quantification, hypocore on T2 map and T1 map strongly correlated (Spearman's r > 0.7, p < 0.001 for both) with IMH extent on T2*w and presented an overall excellent agreement on Bland-Altman analysis. By linear mixed model analysis, absolute hypocore size did not differ among T1-, T2 map, and T2*w. T2/T1 maps had the best intra- and inter-observer reproducibility among CMR techniques. CONCLUSION: Hypocore on T2/T1 map is the best alternative technique to T2*w for diagnosing and quantifying IMH in post-STEMI patients. KEY POINT: • Mapping techniques are the best alternatives for diagnosing post-infarction intramyocardial haemorrhage. • Mapping techniques are valuable tools for imaging intramyocardial haemorrhage.

3D whole-heart grey-blood late gadolinium enhancement cardiovascular magnetic resonance imaging.

PURPOSE: To develop a free-breathing whole-heart isotropic-resolution 3D late gadolinium enhancement (LGE) sequence with Dixon-encoding, which provides co-registered 3D grey-blood phase-sensitive inversion-recovery (PSIR) and complementary 3D fat volumes in a single scan of < 7 min. METHODS: A free-breathing 3D PSIR LGE sequence with dual-echo Dixon readout with a variable density Cartesian trajectory with acceleration factor of 3 is proposed. Image navigators are acquired to correct both inversion recovery (IR)-prepared and reference volumes for 2D translational respiratory motion, enabling motion compensated PSIR reconstruction with 100% respiratory scan efficiency. An intermediate PSIR reconstruction is performed between the in-phase echoes to estimate the signal polarity which is subsequently applied to the IR-prepared water volume to generate a water grey-blood PSIR image. The IR-prepared water volume is obtained using a water/fat separation algorithm from the corresponding dual-echo readout. The complementary fat-volume is obtained after water/fat separation of the reference volume. Ten patients (6 with myocardial scar) were scanned with the proposed water/fat grey-blood 3D PSIR LGE sequence at 1.5 T and compared to breath-held grey-blood 2D LGE sequence in terms of contrast ratio (CR), contrast-to-noise ratio (CNR), scar depiction, scar transmurality, scar mass and image quality. RESULTS: Comparable CRs (p = 0.98, 0.40 and 0.83) and CNRs (p = 0.29, 0.40 and 0.26) for blood-myocardium, scar-myocardium and scar-blood respectively were obtained with the proposed free-breathing 3D water/fat LGE and 2D clinical LGE scan. Excellent agreement for scar detection, scar transmurality, scar mass (bias = 0.29%) and image quality scores (from 1: non-diagnostic to 4: excellent) of 3.8 ± 0.42 and 3.6 ± 0.69 (p > 0.99) were obtained with the 2D and 3D PSIR LGE approaches with comparable total acquisition time (p = 0.29). Similar agreement in intra and inter-observer variability were obtained for the 2D and 3D acquisition respectively. CONCLUSION: The proposed approach enabled the acquisition of free-breathing motion-compensated isotropic-resolution 3D grey-blood PSIR LGE and fat volumes. The proposed approach showed good agreement with conventional 2D LGE in terms of CR, scar depiction and scan time, while enabling free-breathing acquisition, whole-heart coverage, reformatting in arbitrary views and visualization of both water and fat information.

Clinical comparison of sub-mm high-resolution non-contrast coronary CMR angiography against coronary CT angiography in patients with low-intermediate risk of coronary artery disease: a single center trial.

BACKGROUND: The widespread clinical application of coronary cardiovascular magnetic resonance (CMR) angiography (CMRA) for the assessment of coronary artery disease (CAD) remains limited due to low scan efficiency leading to prolonged and unpredictable acquisition times; low spatial-resolution; and residual respiratory motion artefacts resulting in limited image quality. To overcome these limitations, we have integrated highly undersampled acquisitions with image-based navigators and non-rigid motion correction to enable high resolution (sub-1 mm3) free-breathing, contrast-free 3D whole-heart coronary CMRA with 100% respiratory scan efficiency in a clinically feasible and predictable acquisition time. OBJECTIVES: To evaluate the diagnostic performance of this coronary CMRA framework against coronary computed tomography angiography (CTA) in patients with suspected CAD. METHODS: Consecutive patients (n = 50) with suspected CAD were examined on a 1.5T CMR scanner. We compared the diagnostic accuracy of coronary CMRA against coronary CTA for detecting a ≥ 50% reduction in luminal diameter. RESULTS: The 50 recruited patients (55 ± 9 years, 33 male) completed coronary CMRA in 10.7 ± 1.4 min. Twelve (24%) had significant CAD on coronary CTA. Coronary CMRA obtained diagnostic image quality in 95% of all, 97% of proximal, 97% of middle and 90% of distal coronary segments. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were: per patient (100%, 74%, 55%, 100% and 80%), per vessel (81%, 88%, 46%, 97% and 88%) and per segment (76%, 95%, 44%, 99% and 94%) respectively. CONCLUSIONS: The high diagnostic image quality and diagnostic performance of coronary CMRA compared against coronary CTA demonstrates the potential of coronary CMRA as a robust and safe non-invasive alternative for excluding significant disease in patients at low-intermediate risk of CAD.

CarDiac magnEtic Resonance for prophylactic Implantable-cardioVerter defibrillAtor ThErapy in Non-Ischaemic dilated CardioMyopathy: an international Registry.

AIMS: The aim of this registry was to evaluate the additional prognostic value of a composite cardiac magnetic resonance (CMR)-based risk score over standard-of-care (SOC) evaluation in a large cohort of consecutive unselected non-ischaemic cardiomyopathy (NICM) patients. METHODS AND RESULTS: In the DERIVATE registry (www.clinicaltrials.gov/registration: RCT#NCT03352648), 1000 (derivation cohort) and 508 (validation cohort) NICM patients with chronic heart failure (HF) and left ventricular ejection fraction <50% were included. All-cause mortality and major adverse arrhythmic cardiac events (MAACE) were the primary and secondary endpoints, respectively. During a median follow-up of 959 days, all-cause mortality and MAACE occurred in 72 (7%) and 93 (9%) patients, respectively. Age and >3 segments with midwall fibrosis on late gadolinium enhancement (LGE) were the only independent predictors of all-cause mortality (HR: 1.036, 95% CI: 1.0117-1.056, P < 0.001 and HR: 2.077, 95% CI: 1.211-3.562, P = 0.008, respectively). For MAACE, the independent predictors were male gender, left ventricular end-diastolic volume index by CMR (CMR-LVEDVi), and >3 segments with midwall fibrosis on LGE (HR: 2.131, 95% CI: 1.231-3.690, P = 0.007; HR: 3.161, 95% CI: 1.750-5.709, P < 0.001; and HR: 1.693, 95% CI: 1.084-2.644, P = 0.021, respectively). A composite clinical and CMR-based risk score provided a net reclassification improvement of 63.7% (P < 0.001) for MAACE occurrence when added to the model based on SOC evaluation. These findings were confirmed in the validation cohort. CONCLUSION: In a large multicentre, multivendor cohort registry reflecting daily clinical practice in NICM work-up, a composite clinical and CMR-based risk score provides incremental prognostic value beyond SOC evaluation, which may have impact on the indication of implantable cardioverter-defibrillator implantation.

Evaluation of accelerated motion-compensated 3d water/fat late gadolinium enhanced MR for atrial wall imaging.

OBJECTIVE: 3D late gadolinium enhancement (LGE) imaging is a promising non-invasive technique for the assessment of atrial fibrosis. However, current techniques result in prolonged and unpredictable scan times and high rates of non-diagnostic images. The purpose of this study was to compare the performance of a recently proposed accelerated respiratory motion-compensated 3D water/fat LGE technique with conventional 3D LGE for atrial wall imaging. MATERIALS AND METHODS: 18 patients (age: 55.7±17.1 years) with atrial fibrillation underwent conventional diaphragmatic navigator gated inversion recovery (IR)-prepared 3D LGE (dNAV) and proposed image-navigator motion-corrected water/fat IR-prepared 3D LGE (iNAV) imaging. Images were assessed for image quality and presence of fibrosis by three expert observers. The scan time for both techniques was recorded. RESULTS: Image quality scores were improved with the proposed compared to the conventional method (iNAV: 3.1 ± 1.0 vs. dNAV: 2.6 ± 1.0, p = 0.0012, with 1: Non-diagnostic to 4: Full diagnostic). Furthermore, scan time for the proposed method was significantly shorter with a 59% reduction is scan time (4.5 ± 1.2 min vs. 10.9 ± 3.9 min, p < 0.0001). The images acquired with the proposed method were deemed as inconclusive less frequently than the conventional images (expert 1/expert 2: 4/7 dNAV and 2/4 iNAV images inconclusive). DISCUSSION: The motion-compensated water/fat LGE method enables atrial wall imaging with diagnostic quality comparable to the current conventional approach with a significantly shorter scan of about 5 min.

Isotropic 3D Cartesian single breath-hold CINE MRI with multi-bin patch-based low-rank reconstruction.

PURPOSE: To develop a novel acquisition and reconstruction framework for isotropic 3D Cartesian cardiac CINE within a single breath-hold for left ventricle (LV) and whole-heart coverage. METHODS: A variable-density Cartesian acquisition with spiral profile ordering, out-inward sampling, and acquisition-adaptive alternating tiny golden/golden angle increment between spiral arms is proposed to provide incoherent and nonredundant sampling within and among cardiac phases. A novel multi-bin patch-based low-rank reconstruction, named MB-PROST, is proposed to exploit redundant information on a local (within a patch), nonlocal (similar patches within a spatial neighborhood), and temporal (among all cardiac phases) scale with an implicit motion alignment among patches. The proposed multi-bin patch-based low-rank reconstruction reconstruction is compared against compressed sensing reconstruction, whereas LV function parameters derived from the proposed 3D CINE framework are compared against those estimated from conventional multislice 2D CINE imaging in 10 healthy subjects and 15 patients. RESULTS: The proposed framework provides 3D cardiac CINE images with high spatial (1.9 mm3 ) and temporal resolution (˜50 ms) in a single breath-hold of Ëœ20 s for LV and Ëœ26 s for whole-heart coverage in healthy subjects. Shorter breath-hold durations of Ëœ13 to 15 s are feasible for LV coverage with slightly anisotropic resolution (1.9 × 1.9 × 2.5 mm) in patients. LV function parameters derived from 3D CINE were in good agreement with 2D CINE, with a bias of -0.1 mL/0.1 mL, -0.9 mL/-1.0 mL, -0.1%/-0.8%; and confidence intervals of ±1.7 mL/±3.7 mL, ±1.2 mL/±2.6 mL, and ±1.2%/±3.6% (10 healthy subjects/15 patients) for end-systolic volume, end-diastolic volume, and ejection fraction, respectively. CONCLUSION: The proposed framework enables 3D isotropic cardiac CINE in a single breath-hold scan of Ëœ20 s/˜26 s for LV/whole-heart coverage, showing good agreement with clinical 2D CINE scans in terms of LV functional assessment.

Multi-parametric liver tissue characterization using MR fingerprinting: Simultaneous T1 , T2 , T2 *, and fat fraction mapping.

PURPOSE: Quantitative T1 , T2 , T2 *, and fat fraction (FF) maps are promising imaging biomarkers for the assessment of liver disease, however these are usually acquired in sequential scans. Here we propose an extended MR fingerprinting (MRF) framework enabling simultaneous liver T1 , T2 , T2 *, and FF mapping from a single ~14 s breath-hold scan. METHODS: A gradient echo (GRE) liver MRF sequence with nine readouts per TR, low flip angles (5-15°), varying magnetisation preparation and golden angle radial trajectory is acquired at 1.5T to encode T1 , T2 , T2 *, and FF simultaneously. The nine-echo time-series are reconstructed using a low-rank tensor constrained reconstruction and used to fit T2 *, B0 and to separate the water and fat signals. Water- and fat-specific T1 , T2, and M0 are obtained through dictionary matching, whereas FF estimation is extracted from the M0 maps. The framework was evaluated in a standardized T1 /T2 phantom, a water-fat phantom, and 12 subjects in comparison to reference methods. Preliminary clinical feasibility is shown in four patients. RESULTS: The proposed water T1 , water T2 , T2 *, and FF maps in phantoms showed high coefficients of determination (r2 > 0.97) relative to reference methods. Measured liver MRF values in vivo (mean ± SD) for T1 , T2 , T2 *, and FF were 671 ± 60 ms, 43.2 ± 6.8 ms, 29 ± 6.6 ms, and 3.2 ± 2.6% with biases of 92 ms, -7.1 ms, -1.4 ms, and 0.63% when compared to conventional methods. CONCLUSION: A nine-echo liver MRF sequence allows for quantitative multi-parametric liver tissue characterization in a single breath-hold scan of ~14 s. Future work will aim to validate the proposed approach in patients with liver disease.