Late Gadolinium Enhancement Cardiac Magnetic Resonance Imaging: From Basic Concepts to Emerging Methods

Holtackers R.J., Van De Heyning C.M., Chiribiri A., Wildberger J.E., Botnar R.M., Kooi M.E.

For almost 20 years, late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been the reference standard for the non-invasive assessment of myocardial viability. Since the blood pool often appears equally bright as the enhanced scar regions, detection of subendocardial scar patterns can be challenging. Various novel LGE methods have been proposed that null or suppress the blood signal by employing additional magnetization preparation mechanisms. This review aims to provide a comprehensive overview of these dark-blood LGE methods, discussing the magnetization preparation schemes and findings in phantom, preclinical, and clinical studies. Finally, conclusions on the current evidence and limitations are drawn and new avenues for future research are discussed. Dark-blood LGE methods are a promising new tool for non-invasive assessment of myocardial viability. For a mainstream adoption of dark-blood LGE, however, clinical availability and ease of use are crucial.

Holtackers R.J., Wildberger J.E., Wintersperger B.J., Chiribiri A.

Cardiac magnetic resonance imaging (MRI) is widely applied for the noninvasive assessment of cardiac structure and function, and for tissue characterization. For more than 2 decades, 1.5 T has been considered the field strength of choice for cardiac MRI. Although the number of 3-T systems significantly increased in the past 10 years and numerous new developments were made, challenges seem to remain that hamper a widespread clinical use of 3-T MR systems for cardiac applications. As the number of clinical cardiac applications is increasing, with each having their own benefits at both field strengths, no "holy grail" field strength exists for cardiac MRI that one should ideally use. This review describes the physical differences between 1.5 and 3 T, as well as the effect of these differences on major (routine) cardiac MRI applications, including functional imaging, edema imaging, late gadolinium enhancement, first-pass stress perfusion, myocardial mapping, and phase contrast flow imaging. For each application, the advantages and limitations at both 1.5 and 3 T are discussed. Solutions and alternatives are provided to overcome potential limitations. Finally, we briefly elaborate on the potential use of alternative field strengths (ie, below 1.5 T and above 3 T) for cardiac MRI and conclude with field strength recommendations for the future of cardiac MRI.

Munoz C., Sim I., Neji R., Kunze K.P., Masci P., Schmidt M., O’Neill M., Williams S., Botnar R.M., Prieto C.

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. 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. 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). 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.

Holtackers R.J., Gommers S., Heckman L.I., Van De Heyning C.M., Chiribiri A., Prinzen F.W.

Conventional bright-blood late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (MRI) often suffers from poor scar-to-blood contrast due to the bright blood pool adjacent to the enhanced scar tissue. Recently, a dark-blood LGE method was developed which increases scar-to-blood contrast without using additional magnetization preparation.We aim to histopathologically validate this dark-blood LGE method in a porcine animal model with induced myocardial infarction (MI).Prospective.Thirteen female Yorkshire pigs.1.5 T, two-dimensional phase-sensitive inversion-recovery radiofrequency-spoiled turbo field-echo.MI was experimentally induced by transient coronary artery occlusion. At 1-week and 7-week post-infarction, in-vivo cardiac MRI was performed including conventional bright-blood and novel dark-blood LGE. Following the second MRI examination, the animals were sacrificed, and histopathology was obtained. Matching LGE slices and histopathology samples were selected based on anatomical landmarks. Independent observers, while blinded to other data, manually delineated the endocardial, epicardial, and infarct borders on either LGE images or histopathology samples. The percentage of infarcted left-ventricular myocardium was calculated for both LGE methods on a per-slice basis, and compared with histopathology as reference standard. Contrast-to-noise ratios were calculated for both LGE methods at 1-week and 7-week post-infarction.Pearson's correlation coefficient and paired-sample t-tests were used. Significance was set at P < 0.05.A combined total of 24 matched LGE and histopathology slices were available for histopathological validation. Dark-blood LGE demonstrated a high level of agreement compared to histopathology with no significant bias (-0.03%, P = 0.75). In contrast, bright-blood LGE showed a significant bias of -1.57% (P = 0.03) with larger 95% limits of agreement than dark-blood LGE. Image analysis demonstrated significantly higher scar-to-blood contrast for dark-blood LGE compared to bright-blood LGE, at both 1-week and 7-weeks post-infarction.Dark-blood LGE without additional magnetization preparation provides superior visualization and quantification of ischemic scar compared to the current in vivo reference standard.1 TECHNICAL EFFICACY STAGE: 2.

Dang Y., Hou Y.

Cardiac magnetic resonance imaging (CMR) has proven itself as an accurate and robust diagnostic approach and has been widely used in the detection of various heart diseases. An increasing number of studies focusing more on the prognostic aspect of LGE-CMR arose in recent years, contributing to the redundant systematic reviews and meta-analyses in this field. By providing a bird’s eye view and performing scrupulous evidence rating, this umbrella review aims to help clinical practitioners and policy-makers interpret the results of the meta-analyses on the prognostic role of late gadolinium enhancement (LGE) in patients with heart diseases. An umbrella review of meta-analyses of observational studies. The 11 included systematic reviews comprise 33 meta-analyses covering 11 types of heart diseases, 19 different outcomes, 23,058 subjects, and 5393 events. Thirty-one of 33 meta-analyses were found supported by weak pieces of evidence and the remaining were deemed not suggestive. The meta-analysis with a p value of 9.21 × 10−15 and 991 events was updated by strictly re-conducting the meta-analysis by Becker et al. The updated meta-analysis on the prognostic role of LGE in subjects with non-ischemic dilated cardiomyopathy (DCM) in terms of major adverse cardiovascular events (MACE) included 1131 events and was rated as highly suggestive evidence. The prognostic role of LGE in DCM patients in terms of MACE is supported by highly suggestive evidence, which may facilitate the optimization of the timing of prophylactic implantable or wearable implantable cardioverter-defibrillators (ICD) considering the high risk of MACE and lower expectation of recovery. • Cardiac magnetic resonance imaging (CMR) has been widely used in the detection of various heart diseases. Numerous studies focusing on the prognostic aspect of LGE arose in recent years. • The meta-analysis on the prognostic role of LGE in dilated cardiomyopathy (DCM) patients in terms of major adverse cardiovascular events (MACE) by Becker et al was updated and was deemed to be supported by highly suggestive evidence. • The credibility of the meta-analysis supported by highly suggestive evidence may facilitate the optimization of the timing of prophylactic implantable or wearable implantable cardioverter defibrillators (ICD) considering the high risk of MACE and lower expectation of recovery.

Holtackers R.J., Gommers S., Van De Heyning C.M., Mihl C., Smink J., Higgins D.M., Wildberger J.E., ter Bekke R.M.

Fifty consecutive patients with previous cardiac arrhythmias, scheduled for high-resolution 3D LGE MRI, were prospectively enrolled between October 2017 and February 2020. Free-breathing 3D dark-blood LGE MRI with high isotropic resolution (1.6 × 1.6 × 1.6 mm) was performed using a conventional fixed TI (n = 25) or a dynamic TI (n = 25). The average increase in blood nulling TI per minute was obtained from Look-Locker scans before and after the 3D acquisition in the first fixed TI group. This average increment in TI was used as input to calculate the dynamic increment of the initial blood nulling TI value as set in the second dynamic TI group. Regions of interest were drawn in the left ventricular blood pool to assess mean signal intensity as a measure for blood pool suppression. Overall image quality, observer confidence, and scar demarcation were scored on a 3-point scale.Three-dimensional dark-blood LGE data sets were successfully acquired in 46/50 patients (92%). The calculated average TI increase of 2.3 ± 0.5 ms/min obtained in the first fixed TI group was incorporated in the second dynamic TI group and led to a significant decrease of 72% in the mean blood pool signal intensity compared with the fixed TI group (P < 0.001). Overall image quality (P = 0.02), observer confidence (P = 0.02), and scar demarcation (P = 0.01) significantly improved using a dynamic TI.A steadily increasing dynamic TI improves blood pool suppression for optimized dark-blood contrast and increases observer confidence in free-breathing 3D dark-blood LGE MRI with high isotropic resolution.

Bojer A.S., Sørensen M.H., Vejlstrup N., Goetze J.P., Gæde P., Madsen P.L.

Cardiovascular magnetic resonance imaging (CMR) have described localised non-ischemic late gadolinium enhancement (LGE) lesions of prognostic importance in various non-ischemic cardiomyopathies. Ischemic LGE lesions are prevalent in diabetes (DM), but non-ischemic LGE lesions have not previously been described or systematically studied in DM. 296 patients with type 2 DM (T2DM) and 25 sex-matched control subjects underwent echocardiography and CMR including adenosine-stress perfusion, T1-mapping and LGE. 264 patients and all control subjects completed the CMR protocol. 78.4% of patients with T2DM had no LGE lesions; 11.0% had ischemic LGE lesions only; 9.5% had non-ischemic LGE lesions only; and 1.1% had both one ischemic and one non-ischemic lesion. The non-ischemic LGE lesions were situated mid-myocardial in the basal lateral or the basal inferolateral part of the left ventricle and the affected segments showed normal to high wall thickness and normal contraction. Patients with non-ischemic LGE lesions in comparison with patients without LGE lesions had increased myocardial mass (150 ± 34 vs. 133 ± 33 g, P = 0.02), average E/e’(9.9 IQR8.7–12.6 vs. 8.8 IQR7.4–10.7, P = 0.04), left atrial maximal volume (102 IQR84.6–115.2 vs. 91 IQR75.2–100.0 mL, P = 0.049), NT-proBNP (8.9 IQR5.9–19.7 vs. 5.9 IQR5.9–10.1 µmol/L, P = 0.02) and high-sensitive troponin (15.6 IQR13.0–26.1 vs. 13.0 IQR13.0–14.6 ng/L, P = 0.007) and a higher prevalence of retinopathy (48 vs. 25%, P = 0.009) and autonomic neuropathy (52 vs. 30.5%, P = 0.005). A specific LGE pattern with lesions in the basal lateral or the basal inferolateral part of the left ventricle was found in patients with type 2 diabetes. Trial registration https://www.clinicaltrials.gov . Unique identifier: NCT02684331.

Munoz C., Bustin A., Neji R., Kunze K.P., Forman C., Schmidt M., Hajhosseiny R., Masci P., Zeilinger M., Wuest W., Botnar R.M., Prieto C.

Conventional 2D inversion recovery (IR) and phase sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) have been widely incorporated into routine CMR for the assessment of myocardial viability. However, reliable suppression of fat signal, and increased isotropic spatial resolution and volumetric coverage within a clinically feasible scan time remain a challenge. In order to address these challenges, this work proposes a highly efficient respiratory motion-corrected 3D whole-heart water/fat LGE imaging framework. An accelerated IR-prepared 3D dual-echo acquisition and motion-corrected reconstruction framework for whole-heart water/fat LGE imaging was developed. The acquisition sequence includes 2D image navigators (iNAV), which are used to track the respiratory motion of the heart and enable 100% scan efficiency. Non-rigid motion information estimated from the 2D iNAVs and from the data itself is integrated into a high-dimensional patch-based undersampled reconstruction technique (HD-PROST), to produce high-resolution water/fat 3D LGE images. A cohort of 20 patients with known or suspected cardiovascular disease was scanned with the proposed 3D water/fat LGE approach. 3D water LGE images were compared to conventional breath-held 2D LGE images (2-chamber, 4-chamber and stack of short-axis views) in terms of image quality (1: full diagnostic to 4: non-diagnostic) and presence of LGE findings. Image quality was considered diagnostic in 18/20 datasets for both 2D and 3D LGE magnitude images, with comparable image quality scores (2D: 2.05 ± 0.72, 3D: 1.88 ± 0.90, p-value = 0.62) and overall agreement in LGE findings. Acquisition time for isotropic high-resolution (1.3mm3) water/fat LGE images was 8.0 ± 1.4 min (3-fold acceleration, 60–88 slices covering the whole heart), while 2D LGE images were acquired in 5.6 ± 2.2 min (12–18 slices, including pauses between breath-holds) albeit with a lower spatial resolution (1.40–1.75 mm in-plane × 8 mm slice thickness). A novel framework for motion-corrected whole-heart 3D water/fat LGE imaging has been introduced. The method was validated in patients with known or suspected cardiovascular disease, showing good agreement with conventional breath-held 2D LGE imaging, but offering higher spatial resolution, improved volumetric coverage and good image quality from a free-breathing acquisition with 100% scan efficiency and predictable scan time.

Kirstein B., Morris A., Baher A., Csécs I., Kheirkhahan M., Kaur G., Kholmovski E., Marrouche N.F.

Background Cryoballoon ablation (CBA) for pulmonary vein isolation (PVI) is an established modality for the treatment of atrial fibrillation (AF). We report feasibility of left atrial (LA) substrate modification in addition to PVI both using the cryoballoon. Methods LA substrates and CBA-induced scar were assessed at baseline and 3 months after ablation using late gadolinium enhancement magnetic resonance imaging (LGE-MRI). Common periprocedural data including postablation LGE-MRI for evaluation of esophageal thermal injury, and CBA-associated complications were collected. Freedom from AF recurrence at 12 months was assessed using Holter and 30-day rhythm monitors. Results In 26 patients (64 ± 11 years, 69% male; 27% persistent AF, CHADSVASC score: 2.3 ± 1.5; left ventricular ejection fraction: 56 ± 10%, oral anticoagulation with warfarin/direct oral anticoagulants: n = 11/15), referred for first-time AF ablation, CBA of the pulmonary veins and extrapulmonary LA substrates was performed (median: 12 [interquartile range {IQR}: 7-14] freezes over 1675 seconds [IQR: 1168-2160]). On LGE-MRI, significant postablation cryoballoon-induced LA scar (median: 19.4% [IQR: 13.4-24.7] in comparison to baseline preablation LA-LGE (median: 10.6% [IQR 3.1-13.1]; P = .01) was found. Freedom from AF recurrence at 12 months was 74.5% with median time-to-recurrence of 242 days (IQR: 172-298). In 15 of 26 (58%) patients, esophageal enhancement on the postablation MRI was present with full recovery after 3 months. No major periprocedural complications were observed. Conclusion LA substrate modification in addition to PVI using LGE-MRI-guided CBA is feasible but still experimental. The efficacy and safety have to be investigated in a prospective randomized trial.

Alba A.C., Gaztañaga J., Foroutan F., Thavendiranathan P., Merlo M., Alonso-Rodriguez D., Vallejo-García V., Vidal-Perez R., Corros-Vicente C., Barreiro-Pérez M., Pazos-López P., Perez-David E., Dykstra S., Flewitt J., Pérez-Rivera J.Á., et. al.

Background: Dilated cardiomyopathy is associated with increased risk of major cardiovascular events. Late gadolinium enhancement (LGE) cardiac magnetic resonance imaging is a unique tissue-based marker that, in single-center studies, suggests strong prognostic value. We retrospectively studied associations between LGE presence and adverse cardiovascular events in patients with dilated cardiomyopathy in a multicenter setting as part of an emerging global consortium (MINICOR [Multi-Modal International Cardiovascular Outcomes Registry]). Methods: Consecutive patients with dilated cardiomyopathy referred for cardiac magnetic resonance (2000–2017) at 12 institutions in 4 countries were studied. Using multivariable Cox proportional hazard and semiparametric Fine and Gray models, we evaluated the association between LGE and the composite primary end point of all-cause mortality, heart transplantation, or left ventricular assist device implant and a secondary arrhythmic end point of sudden cardiac death or appropriate implantable cardioverter-defibrillator shock. Results: We studied 1672 patients, mean age 56±14 years (29% female), left ventricular ejection fraction 33±11%, and 25% having New York Heart Association class III to IV; 650 patients (39%) had LGE. During 2.3 years (interquartile range, 1.0–4.3) follow-up, 160 patients experienced the primary end point, and 88 experienced the arrhythmic end point. In multivariable analyses, LGE was associated with 1.5-fold (hazard ratio, 1.45 [95% CI, 1.03–2.04]) risk of the primary end point and 1.8-fold (hazard ratio, 1.82 [95% CI, 1.20–3.06]) risk of the arrhythmic end point. Primary end point risk was increased in patients with multiple LGE patterns, although arrhythmic risk was higher among patients receiving primary prevention implantable cardioverter-defibrillator and widening QRS. Conclusions: In this large multinational study of patients with dilated cardiomyopathy, the presence of LGE showed strong prognostic value for identification of high-risk patients. Randomized controlled trials evaluating LGE-based care management strategies are warranted.

Bustin A., Fuin N., Botnar R.M., Prieto C.

Cardiac magnetic resonance (CMR) imaging is an important tool for the non-invasive assessment of cardiovascular disease. However, CMR suffers from long acquisition times due to the need of obtaining images with high temporal and spatial resolution, different contrasts and/or whole-heart coverage. In addition, both cardiac and respiratory-induced motion of the heart during the acquisition need to be accounted for, further increasing the scan time. Several undersampling reconstruction techniques have been proposed during the last decades to speed up CMR acquisition. These techniques rely on acquiring less data than needed and estimating the non-acquired data exploiting some sort of prior information. Parallel imaging and compressed sensing undersampling reconstruction techniques have revolutionized the field, enabling 2- to 3-fold scan time accelerations to become standard in clinical practice. Recent scientific advances in CMR reconstruction hinge on the thriving field of artificial intelligence. Machine learning reconstruction approaches have been recently proposed to learn the non-linear optimization process employed in CMR reconstruction. Unlike analytical methods for which the reconstruction problem is explicitly defined into the optimization process, machine learning techniques make use of large data sets to learn the key reconstruction parameters and priors. In particular, deep learning techniques promise to use deep neural networks to learn the reconstruction process from existing datasets in advance, providing a fast and efficient reconstruction that can be applied to all newly acquired data. However, before machine learning and deep neural networks can realize their full potentials and enter widespread clinical routine for CMR image reconstruction, there are several technical hurdles that need to be addressed. In this article, we provide an overview of the recent developments in the area of artificial intelligence for CMR image reconstruction. The underlying assumptions of established techniques such as compressed sensing and low-rank reconstruction are briefly summarized, while a greater focus is given to recent advances in dictionary learning and deep learning based CMR reconstruction. In particular, approaches that exploit neural networks as implicit or explicit priors are discussed for 2D dynamic cardiac imaging and 3D whole-heart CMR imaging. Current limitations, challenges and potential future directions of these techniques are also discussed.

Kramer C.M., Barkhausen J., Bucciarelli-Ducci C., Flamm S.D., Kim R.J., Nagel E.

This document is an update to the 2013 publication of the Society for Cardiovascular Magnetic Resonance (SCMR) Board of Trustees Task Force on Standardized Protocols. Concurrent with this publication, 3 additional task forces will publish documents that should be referred to in conjunction with the present document. The first is a document on the Clinical Indications for CMR, an update of the 2004 document. The second task force will be updating the document on Reporting published by that SCMR Task Force in 2010. The 3rd task force will be updating the 2013 document on Post-Processing. All protocols relative to congenital heart disease are covered in a separate document. The section on general principles and techniques has been expanded as more of the techniques common to CMR have been standardized. A section on imaging in patients with devices has been added as this is increasingly seen in day-to-day clinical practice. The authors hope that this document continues to standardize and simplify the patient-based approach to clinical CMR. It will be updated at regular intervals as the field of CMR advances.

Papanastasiou C.A., Kokkinidis D.G., Kampaktsis P.N., Bikakis I., Cunha D.K., Oikonomou E.K., Greenwood J.P., Garcia M.J., Karamitsos T.D.

The aim of this systematic review was to explore the prognostic value of late gadolinium enhancement (LGE) in patients with aortic stenosis (AS). Myocardial fibrosis is a common feature of many cardiac diseases. Cardiac magnetic resonance (CMR) has the ability to noninvasively detect regional fibrosis by using the LGE technique. Several studies have explored whether LGE is associated with adverse outcome in patients with AS. Electronic databases were searched to identify studies investigating the ability of LGE to predict all-cause mortality in patients with AS. A random effects model meta-analysis was conducted. Heterogeneity was assessed with the I 2 statistic. Six studies comprising 1,151 patients met our inclusion criteria. LGE was present in 49.1% of patients with AS. In the pooled analysis, LGE was found to be a strong univariate predictor of all-cause mortality (pooled unadjusted odds ratio: 2.56; 95% confidence interval: 1.83 to 3.57; I 2 = 0%). Four of the included studies reported adjusted hazard ratios for mortality. LGE was independently associated with mortality, even after adjusting for baseline characteristics (pooled adjusted hazard ratio: 2.50; 95% confidence interval: 1.64 to 3.83; I 2 = 0%). Fibrosis on LGE-CMR is a powerful predictor of all-cause mortality in patients with AS and may serve as a novel marker for risk stratification. Future studies should explore whether LGE-CMR can also be used to optimize timing of AS-related interventions.

Fochler F., Yamaguchi T., Kheirkahan M., Kholmovski E.G., Morris A.K., Marrouche N.F.

Background: Macroreentrant atrial tachycardia (AT) accounts for 40% to 60% of recurrent atrial arrhythmias after atrial fibrillation (AF) ablation. To describe late gadolinium enhancement magnetic resonance imaging (LGE-MRI)–detected scar-based dechanneling as new ablation strategy to treat ATs after AF ablation. Methods: Data from 102 patients who underwent initial AF ablation and repeat ablation for recurrent atrial arrhythmia within 1-year follow-up were analyzed. All patients underwent LGE-MRI before initial and repeat ablation. Depending on the recurrent rhythm, patients with AF and AT recurrence were assigned to group 1 or 2, respectively. Group 1 underwent fibrosis homogenization as second procedure. Group 2 underwent LGE-MRI–detected scar-based dechanneling. Both groups underwent reisolation of pulmonary veins if necessary. Results: Forty-six patients (45%) presented with AF, and 56 patients (55%) presented with AT recurrence during follow-up after initial ablation. In the first 25 patients from group 2, the AT was electroanatomically mapped, and a critical isthmus was defined. It was found that those isthmi were located in the regions with nontransmural scarring detected by LGE-MRI. In the last 31 patients from group 2, an empirical LGE-MRI–based dechanneling was performed solely based on the LGE-MRI results. During 1-year follow-up after second ablation, 67% patients in group 1 and 64% patients in group 2 were free from recurrence (log-rank, P =1.000). In group 2, 64% in the electroanatomically guided and 65% in the LGE-MRI dechanneling group were free from recurrence (log-rank, P =0.900). Conclusions: Anatomic targeting of LGE-MRI–detected gaps and superficial atrial scar is feasible and effective to treat recurrent arrhythmias post-AF ablation. Homogenization of existing scar is the appropriate treatment for recurrent AF, whereas dechanneling of existing isthmi seems the right approach for patients recurring with AT.

Mrsic Z., Mousavi N., Hulten E., Bittencourt M.S.

Late gadolinium enhancement (LGE) has become a standard clinical tool to evaluate myocardial fibrosis to define myocardial viability in the context of ischemic myocardial disease. More recently, LGE has also been used to characterize the presence and pattern of fibrosis in nonischemic cardiomyopathies. It yields unique and valuable diagnostic and prognostic insights for myriad nonischemic clinical indications and has become a key part of routine cardiac MR imaging, and a tool to guide treatment. This article reviews the technical aspects of LGE performance and its diagnostic and prognostic implications in nonischemic cardiomyopathy.

Flynn S., Killick D., McDonald K., Dodd J.

Cardiac MRI serves as an indispensable tool for diagnosing and characterizing myocardial pathology. Late gadolinium enhancement (LGE) imaging enables assessing myocardial scar formation and regional fibrosis. Here, we present a case involving a young woman with congenital dilated cardiomyopathy, showcasing LGE along the interventricular septum. This LGE distribution likely arises from altered ventricular hemodynamics secondary to bundle branch block rather than ischemia. This insight has significant implications for guiding clinical management and avoiding unnecessary interventions.

Reisdorf P., Gavrysh J., Ammann C., Fenski M., Kolbitsch C., Lange S., Hennemuth A., Schulz-Menger J., Hadler T.

Abstract Cardiovascular magnetic resonance imaging (CMR) offers state-of-the-art myocardial tissue differentiation. The CMR technique late gadolinium enhancement (LGE) currently provides the noninvasive gold standard for the detection of myocardial fibrosis. Typically, thresholding methods are used for fibrotic scar tissue quantification. A major challenge for standardized CMR assessment is large variations in the estimated scar for different methods. The aim was to improve quality assurance for LGE scar quantification, a multi-reader comparison tool “Lumos” was developed to support quality control for scar quantification methods. The thresholding methods and an exact rasterization approach were implemented, as well as a graphical user interface (GUI) with statistical and case-specific tabs. Twenty LGE cases were considered with half of them including artifacts and clinical results for eight scar quantification methods computed. Lumos was successfully implemented as a multi-level multi-reader comparison software, and differences between methods can be seen in the statistical results. Histograms visualize confounding effects of different methods. Connecting the statistical level with the case level allows for backtracking statistical differences to sources of differences in the threshold calculation. Being able to visualize the underlying groundwork for the different methods in the myocardial histogram gives the opportunity to identify causes for different thresholds. Lumos showed the differences in the clinical results between cases with artifacts and cases without artifacts. A video demonstration of Lumos is offered as supplementary material 1. Lumos allows for a multi-reader comparison for LGE scar quantification that offers insights into the origin of reader differences.

Kuhnt J., Blaszczyk E., Krüger L.D., Grassow L., Prieto C., Botnar R., Kunze K.P., Schmidt M., Viezzer D.S., Hadler T., Fenski M., Schulz-Menger J.

Pradella M., Elbaz M.S., Lee D.C., Hong K., Passman R.S., Kholmovski E., Peters D.C., Baraboo J.J., Herzka D.A., Nezafat R., Edelman R.R., Kim D.

de Schellenberger A.A., Bergs J., Sack I., Taupitz M.

All tissues and organs are composed of cells and extracellular matrix (ECM). The components of the ECM have important functional and structural roles in tissues. On the one hand, the ECM often dominates the biomechanical properties of soft tissues and provides mechanical support to the tissue. On the other hand, ECM components maintain tissue homeostasis, pH, hydration of the micromilieu, and, via signal transduction, play a key role in ECM-cell interactions, which in turn control cell migration, differentiation, growth, and death. Inflammation, fibrosis, tumor invasion, and injury are associated with the transition of the ECM from homeostasis to remodeling that can dramatically alter the biochemical and biomechanical properties of ECM components. Hence, it is possible to detect and characterize diseases by sensing biochemical and biomechanical changes in the ECM when appropriate imaging methods are used. This chapter discusses the potential of ECM-directed magnetic resonance imaging based on contrast agents and elastography from a clinical radiological perspective in a variety of diseases including atherosclerosis, cardiomyopathy, inflammation, and liver fibrosis.

Rajah M.R., Doubell A.F., Herbst P.G.

Aortic stenosis (AS) is associated with the development of replacement myocardial fibrosis/scar. Given the dose-dependent relationship between scar and clinical outcomes after aortic valve replacement (AVR) surgery, scar quantity may serve as an important risk-stratification tool to aid decision-making on the optimal timing of AVR. Scar is non-invasively assessed and quantified by cardiovascular magnetic resonance (CMR) imaging. Several quantification techniques exist, and consensus on the optimal technique is lacking. These techniques range from a visual manual method to fully automated ones. This review describes the different scar quantification techniques used and highlights their strengths and shortfalls within the context of AS. The two most commonly used techniques in AS include the semi-automated signal threshold versus reference mean (STRM) and full-width half-maximum (FWHM) techniques. The accuracy and reproducibility of these techniques may be hindered in AS by the coexistence of diffuse interstitial fibrosis and the presence of relatively small, non-bright scars. The validation of these techniques against histology, which is the current gold standard for scar quantification in AS, is limited. Based on the best current evidence, the STRM method using a threshold of three standard deviations above the mean signal intensity of remote myocardium is recommended. The high reproducibility of the FWHM technique in non-AS cohorts has been shown and merits further evaluation within the context of AS. Future directions include the use of quantitative T1 mapping for the detection and quantification of scar, as well as the development of serum biomarkers that reflect the fibrotic status of the myocardium in AS.

Ueda J., Kurata H., Ota M., Yabata I., Itagaki K., Sawaya R., Murata C., Banura N., Nishida H., Saito S.

Late gadolinium enhancement (LGE) is a widely used magnetic resonance imaging method for assessing cardiac disease. However, the relationship between different LGE signal thresholds and microscopic tissue staining images is unclear. In this study, we performed cardiovascular MRI on myocardial infarction (MI) model rats and evaluated the relationship between LGE with different signal thresholding methods and tissue staining images. We prepared 16 rats that underwent MRI 14–18 days following a surgery to create an MI model. We captured cine and LGE images of the cardiac short-axis and longitudinal two- and four-chamber views. The mean ± 2SD, ± 3SD, and ± 5SD of the pixel values in the non-infarcted area were defined as the LGE area. We compared areas of Sirius red staining, determined by the color tone, with their respective LGE areas at end-diastole and end-systole. We observed that the LGE area calculated as the mean ± 2SD of the non-infarcted area at end-diastole demonstrated a significant positive correlation with the area of Sirius red staining (Pearson’s correlation coefficient in both: 0.81 [p < 0.01]). Therefore, the LGE area calculated as the mean ± 2SD of the non-infarcted area at end-diastole best reflected the MI area in tissue staining.

Karur G.R., Aneja A., Stojanovska J., Hanneman K., Latchamsetty R., Kersting D., Rajiah P.S.

Parillo M., Mallio C.A., Dekkers I.A., Rovira À., van der Molen A.J., Quattrocchi C.C.

The acquisition of images minutes or even hours after intravenous extracellular gadolinium-based contrast agents (GBCA) administration (“Late/Delayed Gadolinium Enhancement” imaging; in this review, further termed LGE) has gained significant prominence in recent years in magnetic resonance imaging. The major limitation of LGE is the long examination time; thus, it becomes necessary to understand when it is worth waiting time after the intravenous injection of GBCA and which additional information comes from LGE. LGE can potentially be applied to various anatomical sites, such as heart, arterial vessels, lung, brain, abdomen, breast, and the musculoskeletal system, with different pathophysiological mechanisms. One of the most popular clinical applications of LGE regards the assessment of myocardial tissue thanks to its ability to highlight areas of acute myocardial damage and fibrotic tissues. Other frequently applied clinical contexts involve the study of the urinary tract with magnetic resonance urography and identifying pathological abdominal processes characterized by high fibrous stroma, such as biliary tract tumors, autoimmune pancreatitis, or intestinal fibrosis in Crohn’s disease. One of the current areas of heightened research interest revolves around the possibility of non-invasively studying the dynamics of neurofluids in the brain (the glymphatic system), the disruption of which could underlie many neurological disorders.

Sheriev S.R., Sidorina A.S., Baev M.S., Ryzhkov A.V., Fokin V.A.

The article is devoted to a review of the most promising MRI techniques in cardiac imaging, as part of personalized medicine.A brief historical and terminological outline is provided, as well as a description of the current state of the problem. The results of promising methods of MR studies are considered. Issues of clinical importance and recommendations for use of the data are discussed.Various approaches to the diagnosis and treatment of the most significant cardiac diseases are summarized.In conclusion, the views and innovativeness of best practices in modern healthcare are summarized.

Wang D., Jasim Taher H., Al-Fatlawi M., Abdullah B.A., Khayatovna Ismailova M., Abedi-Firouzjah R.

AIM: This study assessed the myocardial infarction (MI) using a novel fusion approach (multi-flavored or tensor-based) of multi-parametric cardiac magnetic resonance imaging (CMRI) at four sequences; T1-weighted (T1W) in the axial plane, sense-balanced turbo field echo (sBTFE) in the axial plane, late gadolinium enhancement of heart short axis (LGE-SA) in the sagittal plane, and four-chamber views of LGE (LGE-4CH) in the axial plane. METHODS: After considering the inclusion and exclusion criteria, 115 patients (83 with MI diagnosis and 32 as healthy control patients), were included in the present study. Radiomic features were extracted from the whole left ventricular myocardium (LVM). Feature selection methods were Least Absolute Shrinkage and Selection Operator (Lasso), Minimum Redundancy Maximum Relevance (MRMR), Chi-Square (Chi2), Analysis of Variance (Anova), Recursive Feature Elimination (RFE), and SelectPersentile. The classification methods were Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF). Different metrics, including receiver operating characteristic curve (AUC), accuracy, F1- score, precision, sensitivity, and specificity were calculated for radiomic features extracted from CMR images using stratified five-fold cross-validation. RESULTS: For the MI detection, Lasso (as the feature selection) and RF/LR (as the classifiers) in sBTFE sequences had the best performance (AUC: 0.97). All features and classifiers of T1 + sBTFE sequences with the weighted method (as the fused image), had a good performance (AUC: 0.97). In addition, the results of the evaluated metrics, especially mean AUC and accuracy for all models, determined that the T1 + sBTFE-weighted fused method had strong predictive performance (AUC: 0.93±0.05; accuracy: 0.93±0.04), followed by T1 + sBTFE-PCA fused method (AUC: 0.85±0.06; accuracy: 0.84±0.06). CONCLUSION: Our selected CMRI sequences demonstrated that radiomics analysis enables to detection of MI accurately. Among the investigated sequences, the T1 + sBTFE-weighted fused method with the highest AUC and accuracy values was chosen as the best technique for MI detection.

Brendel J.M., Holtackers R.J., Geisel J.N., Kübler J., Hagen F., Gawaz M., Nikolaou K., Greulich S., Krumm P.

(1) Background and Objectives: Dark-blood late gadolinium enhancement has been shown to be a reliable cardiac magnetic resonance (CMR) method for assessing viability and depicting myocardial scarring in ischemic cardiomyopathy. The aim of this study was to evaluate dark-blood LGE imaging compared with conventional bright-blood LGE for the detection of myocardial scarring in non-ischemic cardiomyopathies. (2) Materials and Methods: Patients with suspected non-ischemic cardiomyopathy were prospectively enrolled in this single-centre study from January 2020 to March 2023. All patients underwent 1.5 T CMR with both dark-blood and conventional bright-blood LGE imaging. Corresponding short-axis stacks of both techniques were analysed for the presence, distribution, pattern, and localisation of LGE, as well as the quantitative scar size (%). (3) Results: 343 patients (age 44 ± 17 years; 124 women) with suspected non-ischemic cardiomyopathy were examined. LGE was detected in 123 of 343 cases (36%) with excellent inter-reader agreement (κ 0.97–0.99) for both LGE techniques. Dark-blood LGE showed a sensitivity of 99% (CI 98–100), specificity of 99% (CI 98–100), and an accuracy of 99% (CI 99–100) for the detection of non-ischemic scarring. No significant difference in total scar size (%) was observed. Dark-blood imaging with mean 5.35 ± 4.32% enhanced volume of total myocardial volume, bright-blood with 5.24 ± 4.28%, p = 0.84. (4) Conclusions: Dark-blood LGE imaging is non-inferior to conventional bright-blood LGE imaging in detecting non-ischemic scarring. Therefore, dark-blood LGE imaging may become an equivalent method for the detection of both ischemic and non-ischemic scars.

Yin X., Yin X., Pan X., Zhang J., Fan X., Li J., Zhai X., Jiang L., Hao P., Wang J., Chen Y.

Cardiac fibrosis plays an indispensable role in cardiac tissue homeostasis and repair after myocardial infarction (MI). The cardiac fibroblast-to-myofibroblast differentiation and extracellular matrix collagen deposition are the hallmarks of cardiac fibrosis, which are modulated by multiple signaling pathways and various types of cells in time-dependent manners. Our understanding of the development of cardiac fibrosis after MI has evolved in basic and clinical researches, and the regulation of fibrotic remodeling may facilitate novel diagnostic and therapeutic strategies, and finally improve outcomes. Here, we aim to elaborate pathophysiology, examination and intervention of cardiac fibrosis after MI.

Stoks J., Hermans B.J., Boukens B.J., Holtackers R.J., Gommers S., Kaya Y.S., Vernooy K., Cluitmans M.J., Volders P.G., ter Bekke R.M.

IntroductionPatients with ventricular tachyarrhythmias (VT) are at high risk of sudden cardiac death. When appropriate, catheter ablation is modestly effective, with relatively high VT recurrence and complication rates. Personalized models that incorporate imaging and computational approaches have advanced VT management. However, 3D patient-specific functional electrical information is typically not considered. We hypothesize that incorporating non-invasive 3D electrical and structural characterization in a patient-specific model improves VT-substrate recognition and ablation targeting.Materials and methodsIn a 53-year-old male with ischemic cardiomyopathy and recurrent monomorphic VT, we built a structural-functional model based on high-resolution 3D late-gadolinium enhancement (LGE) cardiac magnetic resonance imaging (3D-LGE CMR), multi-detector computed tomography (CT), and electrocardiographic imaging (ECGI). Invasive data from high-density contact and pace mapping obtained during endocardial VT-substrate modification were also incorporated. The integrated 3D electro-anatomic model was analyzed off-line.ResultsMerging the invasive voltage maps and 3D-LGE CMR endocardial geometry led to a mean Euclidean node-to-node distance of 5 ± 2 mm. Inferolateral and apical areas of low bipolar voltage (&lt;1.5 mV) were associated with high 3D-LGE CMR signal intensity (&gt;0.4) and with higher transmurality of fibrosis. Areas of functional conduction delay or block (evoked delayed potentials, EDPs) were in close proximity to 3D-LGE CMR-derived heterogeneous tissue corridors. ECGI pinpointed the epicardial VT exit at ∼10 mm from the endocardial site of origin, both juxtaposed to the distal ends of two heterogeneous tissue corridors in the inferobasal left ventricle. Radiofrequency ablation at the entrances of these corridors, eliminating all EDPs, and at the VT site of origin rendered the patient non-inducible and arrhythmia-free until the present day (20 months follow-up). Off-line analysis in our model uncovered dynamic electrical instability of the LV inferolateral heterogeneous scar region which set the stage for an evolving VT circuit.Discussion and conclusionWe developed a personalized 3D model that integrates high-resolution structural and electrical information and allows the investigation of their dynamic interaction during arrhythmia formation. This model enhances our mechanistic understanding of scar-related VT and provides an advanced, non-invasive roadmap for catheter ablation.

Fu W., Zhao Y., Zhang K., Dai Q., Biekan J., Zheng J., Dong R., Mu J.

Drawing on accumulated patient data from a hospital database, the goal of this retrospective study was to analyze cardiac function associated with global preoperative myocardial scarring assessed by cardiac magnetic resonance with late gadolinium enhancement (CMR-LGE) in patients with ischemic cardiomyopathy (ICM) after coronary artery bypass grafting (CABG).A total of 57 patients diagnosed with ICM who underwent isolated CABG at Beijing Anzhen Hospital between September 2017 and September 2019 were enrolled in this retrospective study. All these patients underwent a preoperative CMR-LGE examination. Based on postoperative echocardiography results at 6 months, cases were divided into the following 2 groups: improved cardiac function [a difference of left ventricular ejection fraction (LVEF) greater than or equal to 5%] and unimproved cardiac function. The factors contributing to these patients' unimproved cardiac function were investigated.At 6 months after surgery, 64.9% (37/57) of cases had improved cardiac function, and 35.1% (20/57) had no improvement. There was no statistical difference between the 2 groups in the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (41.7±7.6 vs. 42.8±8.3; P=0.603), but compared to the improved group, preoperative myocardial scarring was significantly enlarged in the unimproved group (41.9%±6.4% vs. 27.8%±8.5%; P