Late Gadolinium Enhancement Imaging Research Articles

Deep Transfer Learning for Classification of Late Gadolinium Enhancement Cardiac MRI Images into Myocardial Infarction, Myocarditis, and Healthy Classes: Comparison with Subjective Visual Evaluation.

Background/Objectives: To develop a computer-aided diagnosis (CAD) method for the classification of late gadolinium enhancement (LGE) cardiac MRI images into myocardial infarction (MI), myocarditis, and healthy classes using a fine-tuned VGG16 model hybridized with multi-layer perceptron (MLP) (VGG16-MLP) and assess our model's performance in comparison to various pre-trained base models and MRI readers. Methods: This study included 361 LGE images for MI, 222 for myocarditis, and 254 for the healthy class. The left ventricle was extracted automatically using a U-net segmentation model on LGE images. Fine-tuned VGG16 was performed for feature extraction. A spatial attention mechanism was implemented as a part of the neural network architecture. The MLP architecture was used for the classification. The evaluation metrics were calculated using a separate test set. To compare the VGG16 model's performance in feature extraction, various pre-trained base models were evaluated: VGG19, DenseNet121, DenseNet201, MobileNet, InceptionV3, and InceptionResNetV2. The Support Vector Machine (SVM) classifier was evaluated and compared to MLP for the classification task. The performance of the VGG16-MLP model was compared with a subjective visual analysis conducted by two blinded independent readers. Results: The VGG16-MLP model allowed high-performance differentiation between MI, myocarditis, and healthy LGE cardiac MRI images. It outperformed the other tested models with 96% accuracy, 97% precision, 96% sensitivity, and 96% F1-score. Our model surpassed the accuracy of Reader 1 by 27% and Reader 2 by 17%. Conclusions: Our study demonstrated that the VGG16-MLP model permits accurate classification of MI, myocarditis, and healthy LGE cardiac MRI images and could be considered a reliable computer-aided diagnosis approach specifically for radiologists with limited experience in cardiovascular imaging.

Associations between Growth Differentiation Factor 15, Cardiac Troponin T, and N-terminal pro-B-type Natriuretic Peptide, and Future Myocardial Fibrosis Assessed by Cardiac Magnetic Resonance Imaging: Data from the Akershus Cardiac Examination 1950 Study.

Myocardial fibrosis is associated with a poor outcome for patients with cardiovascular disease (CVD). Growth differentiation factor 15 (GDF-15) concentrations predict the risk of death in patients with CVD, but the underlying pathophysiological mechanisms are poorly understood. We aimed to assess the associations between biomarkers of cellular stress and inflammation (GDF-15), cardiac injury (cardiac troponin T [cTnT]), and stretch (N-terminal pro-B-type natriuretic peptide [NT-proBNP]), and subsequent focal and diffuse myocardial fibrosis assessed by cardiac magnetic resonance (CMR) imaging. We measured GDF-15, cTnT, and NT-proBNP in 200 study participants without known coronary artery disease or renal dysfunction from the population-based Akershus Cardiac Examination 1950 Study at baseline in 2012 to 2015. Focal myocardial scars and diffuse fibrosis were assessed by late gadolinium enhancement imaging and septal extracellular volume fraction (ECV) by CMR 4 to 7 years later. The relationships between cardiac biomarkers and CMR parameters were assessed by logistic regression analysis adjusted for common cardiovascular risk factors. The median age was 63.9 (interquartile range 63.4-64.5) years and 49% were women. GDF-15 (adjusted odds ratio [aOR] 4.40, 95% CI 1.09-17.72) and cTnT (aOR 1.59, 95% CI 1.01-2.50) were associated with nonischemic scars in the fully adjusted model. cTnT (aOR 2.45, 95% CI 1.41-4.25) and NT-proBNP (aOR 3.12, 95% CI 1.55-6.28) were associated with ischemic scars. None of the biomarkers were significantly associated with elevated ECV. In a general population cohort, GDF-15, an emerging biomarker of cellular stress and inflammation, associates with nonischemic scars. Biomarkers of myocardial injury and stretch associate with ischemic scars, while no biomarker was associated with diffuse fibrosis as assessed by CMR.

Reliability of post-contrast deep learning-based highly accelerated cardiac cine MRI for the assessment of ventricular function.

The total examination time can be reduced if high-quality two-dimensional (2D) cine images can be collected post-contrast to minimize non-scanning time prior to late gadolinium-enhanced imaging. This study aimed to assess the equivalency of the pre-and post-contrast performance of 2D deep learning-based highly accelerated cardiac cine (DL cine) imaging by evaluating the image quality and the quantification of biventricular volumes and function in the clinical setting. Thirty patients (20 men, mean age 53.7 ± 17.8 years) underwent cardiac magnetic resonance on a 1.5 T scanner for clinical indications, and pre- and post-contrast DL cine images were acquired with a short-axis view. Image-quality was scored according to three main criteria: the blood-to-myocardial contrast, endocardial edge delineation, and presence of motion artifacts throughout the cardiac cycle. Biventricular end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), and left ventricular mass (LVM) were analyzed and compared between the pre- and post-contrast DL cine images. The actual median time of 2D DL cine acquisition was 38.4 ± 9.1 s. There were no significant differences in the image quality scores between pre- and post-contrast DL cine images (p > 0.05). In the volume and functional analysis, there was no significant difference in terms of biventricular EDV, ESV, SV, EF, and LVM (p > 0.05). The performance of 2D DL cine is equivalent before and after contrast injection for the assessment of image quality and ventricular function in the clinical setting.

Safety and therapeutic potential of allogeneic adipose-derived stem cell spray transplantation in ischemic cardiomyopathy: a phase I clinical trial

BackgroundIschemic cardiomyopathy, characterized by coronary artery atherosclerosis, impairs the myocardial tissue. Coronary artery bypass grafting (CABG) is commonly used to revascularize affected areas and improve patient survival rates; however, it can fail to enhance cardiac function. Impaired capillary blood flow may obstruct functional recovery, prompting interest in treatments, such as angiogenic factor administration. Adipose-derived stem cells (ADSCs), which are known for immune evasion, have shown the potential to construct capillary networks and improve myocardial function. This clinical trial aimed to evaluate the safety and efficacy of ADSC spray therapy combined with CABG.MethodsThis single-center, randomized, double-blind study involved patients with ischemic cardiomyopathy who were scheduled for CABG and who had a left ventricular ejection fraction ≤ 40%. The participants were randomized to receive CABG as well as ADSC spray therapy or placebo. The primary endpoints were safety, changes in late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) volumes, and feasibility. The secondary endpoints included left ventricular function, exercise tolerance, and heart failure symptoms.ResultsSeven patients were enrolled; of them, six were randomized to receive ADSC therapy (n = 3) or placebo (n = 3). The procedure was successfully completed with minimal adverse events. One patient in the ADSC group developed pleural effusion that was resolved with drainage. The LGE-MRI volumes decreased in the ADSC group but remained unchanged in the placebo group. Improvements in left ventricular function and exercise tolerance were noted in the ADSC group, with heart failure symptoms improving to New York Heart Association class I. In contrast, the placebo group showed no significant changes, with one patient experiencing worsening symptoms.ConclusionsADSC spray therapy combined with CABG demonstrated safety and efficacy at enhancing cardiac function. ADSC likely contributes to capillary network reconstruction, thereby augmenting the benefits of CABG. Future phase II and III trials are warranted to confirm its therapeutic efficacy and long-term outcomes. This novel approach represents a significant advancement in the treatment of ischemic cardiomyopathy and offers a viable strategy for improving myocardial function and patient prognosis.Trial registration This study was registered with the Japan Registry of Clinical Trials (jRCT2053190103) and ClinicalTrials.gov (NCT04695522)Graphical

Improved myocardial scar visualization using free-breathing motion-corrected wideband black-blood late gadolinium enhancement imaging in patients with implantable cardiac device.

The purpose of this study was to introduce and evaluate a novel two-dimensional wideband black-blood (BB) LGE sequence, incorporating wideband inversion recovery, wideband T2 preparation, and non-rigid motion correction (MOCO) reconstruction, to improve myocardial scar detection and address artifacts associated with implantable cardioverter defibrillators (ICDs). The wideband MOCO free-breathing BB-LGE sequence was tested on a sheep with ischemic scar and in 22 patients with cardiac disease, including 15 with cardiac implants, at 1.5 T. Wideband MOCO free-breathing BB-LGE sequence was compared with conventional and wideband breath-held PSIR-LGE and conventional and wideband breath-held BB-LGE techniques. Image sharpness, entropy, and scar-to-blood, scar-to-myocardium, and blood-to-myocardium contrast were analyzed and reconstruction times were measured. Two expert readers assessed the image quality, ICD artifact severity, and the diagnostic confidence with scar extent. Finally, for the animal study, histopathological assessment of the heart was performed to confirm the presence and localization of scar tissue. In the animal, wideband MOCO free-breathing BB-LGE were reconstructed in 0.6 s and demonstrated a 200 % improvement in scar-to-blood contrast compared to wideband breath-held PSIR-LGE, with significant improvement in image sharpness and reduction in entropy. It also effectively minimized ICD artifacts and accurately detected scars. In patients, wideband MOCO free-breathing BB-LGE were reconstructed in 1.5 ± 0.4 (standard deviation) s per slice. Seventeen patients (17/22; 77 %) with myocardial scars were confidently diagnosed with wideband MOCO free-breathing BB-LGE, compared to 11 (11/22; 50 %) with wideband breath-held PSIR-LGE (P < 0.01). Free-breathing wideband T2-prepared black-blood LGE imaging, combined with motion-corrected reconstruction, offers a promising diagnostic approach for the evaluation of myocardial lesions in patients with ICDs.

Coexistent pleural effusion is found to be associated with aggravated subclinical myocardial injury in systemic lupus erythematous using cardiovascular magnetic resonance imaging.

Pleural effusion (PE) is a common pulmonary manifestation in patients with systemic lupus erythematosus (SLE), and is associated with disease activity. However, little is known regarding the additive effects of PE on cardiac function. Therefore, this study aimed to investigate multi-parameter cardiovascular magnetic resonance imaging (CMR) findings in SLE patients with PE and to explore whether cardiac involvement is associated with PE. Patients with SLE and age-matched/sex-matched healthy controls were included in this study. Patients with SLE were diagnosed according to the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria. Moreover, the PE diagnosis was based on computed tomography, and the height of the effusion was > 5mm. All enrolled individuals underwent CMR imaging, including cine and late gadolinium enhancement (LGE), T1, and T2 mapping imaging. The left and right ventricular function, LGE, T1, extracellular volume (ECV), and T2 values were evaluated. A total of 111 patients with SLE were enrolled, of whom 26 (23.42%) had PE. White cell count, hemoglobin, CRP, ESR, and lactate dehydrogenase levels were higher in SLE patients with PE than in SLE patients without PE (P<0.05). LGE was more prevalent in SLE patients with PE compared with those without PE (P<0.001). In addition, Native T1 (1348 ± 65 ms vs. 1284 ± 67 ms vs. 1261 ± 41 ms; P<0.001), ECV (31.92 ± 4.16% vs. 28.61 ± 3.60% vs. 26.54 ± 2.94%; P<0.001), and T2 (44.76 ± 3.68 ms vs. 41.96 ± 3.62 ms vs. 39.21 ± 2.85 ms; P<0.001) values were high in SLE patients with PE, intermediate in SLE patients without PE, and the lowest in the control group. Linear regression analysis demonstrated that PE was independently associated with LGE (β=0.329; P<0.05), T1 (β=0.346; P<0.05), ECV (β=0.353; P<0.05), and T2 (β=0.201; P<0.05). SLE patients with PE have a higher prevalence of LGE and more diffuse myocardial fibrosis and edema than SLE patients without PE. Moreover, PE is associated with increased diffuse interstitial fibrosis and edema.

Abstract 4138281: Relationship of Collagen Metabolism Biomarkers, Left Atrial Fibrosis and Ablation Outcome in Atrial Fibrillation

Introduction: Inflammation and fibrinogenesis in the left atrium are hypothesized to play a major role in the development of atrial fibrillation (AF). We previously showed that collagen metabolism biomarkers (CMB) are significantly elevated in patients with AF compared to healthy controls. Objective: We sought to investigate the relationship between CMB, Left Atrial Fibrosis (LAF) and AF recurrence after ablation. Methods: Patients with AF undergoing ablation evaluation (N= 96) were prospectively enrolled between 2015 – 2020. Plasma samples were collected prior to ablation and analyzed for CMB using commercially available ELISA kits. Sixty-four patients underwent AF ablation and were followed for 6 months for AF recurrence. CMR was performed in 48 patients using cine and 3D high resolution, late gadolinium enhancement imaging on 3T MRI to measure LAF. Patients were classified into 2 groups dichotomized by the median LAF value. Results: Mean age was 60.3 ± 10.3 years, mean BMI 29.7 ± 4.9 kg/m2, mean CHA2DS2-VASc score 1.9 ± 1.4 and 27% were women. Paroxysmal AF was present in 52.5%. The median LAF score was 13.6% (IQR 9.8 – 21.7). High PINP, high CITP and low TIMP-2 were associated with high LAF score (Table 1). High CITP was also associated with recurrence of AF after ablation {4.26 ng/ml (IQR 3.22 - 4.65) vs 3.26 ng/ml (IQR1.92 - 4.25), P = 0.02}. Conclusion: Higher levels of PINP and CITP were significantly associated with higher LAF score in AF patients. TIMP-2 was associated with low LAF. Higher CITP was also associated with AF recurrence after ablation. Further larger studies are needed to better understand the relationship between collagen biomarkers, LA fibrosis and their clinical impact on rhythm control in AF.

Abstract 4136412: Quantitative Cardiac Magnetic Resonance Standardized Signal Intensity Comparison in Dilated Cardiomyopathy versus Cardiac Sarcoidosis

Introduction/Background: Dilated cardiomyopathy (DCM) and cardiac sarcoidosis (CS) manifest unique late gadolinium enhancement (LGE) patterns on cardiac magnetic resonance (CMR), indicative of differing distributions of myocardial scar tissue. Nevertheless, these LGE patterns lack specificity, leading to significant overlap between the two conditions. Goals/Aims: This study seeks to introduce a novel quantitative method employing z-score analysis of LGE-CMR signal intensity to objectively evaluate and compare the spatial distribution of LGE intensity between DCM and CS. Methods/Approach: The retrospective cohort included 22 NICM patients (13 DCM, 9 CS) that underwent pre-procedural CMR prior to ventricular tachycardia (VT) ablation between November 2018 to May 2023. LGE images were delineated into sub-endocardial, mid-myocardial, and sub-epicardial layers, categorized into anterior, lateral, inferior, and septal walls based on the AHA 17 segment model for LV myocardial segmentation. CMR signal intensities were standardized as z-scores: z = (x−μ)/σ, where x is the MRI signal intensity for a specific myocardial segment and layer, and μ and σ are the mean and standard deviation across all myocardial segments and layers of the LV, to characterize regional intensity variations. Results/Data: Compared to patients with DCM, those with CS exhibited significantly higher CMR signal intensity z-scores in the septum (β=0.32, p=0.009), particularly in the endocardial third of the right ventricular side (β=0.56, p=0.001). A z-score greater than 0.40 in this area was associated with a CS diagnosis, with an area under the ROC curve of 0.692 in 5-fold cross-validation. Conclusions: Patients with CS exhibit higher affinity for contrast in the septum, particularly on the RV endocardium. Standardized analysis of CMR signal intensities provides a novel, quantitative method for distinguishing CS from DCM, with the former exhibiting higher CMR signal intensity z-scores in the septum.

Abstract 4134729: Quantitative, time-efficient viability cardiac magnetic resonance with delayed-phase dynamic contrast enhancement model: a pilot study in dogs with myocardial infarction

Introduction: Late gadolinium enhancement (LGE) is the gold standard for myocardial viability imaging, recommended by all major cardiology societies. In this study, we aimed to develop a time-efficient viability imaging technique utilizing a dynamic contrast enhancement(dDCE) model to shorten the LGE wait time, provide quantitative measures of the contrast washout procedure, and potentially enable a fast and quantitative mean for scar imaging. Methods: A canine study(n=10) was conducted on reperfused myocardial infarction(MI). A dDCE model using dynamic post-contrast T1 maps was adopted to depict the contrast washout process. dDCE maps were reconstructed using the whole dataset(dDCE 30min ) and a 5-minute subset of the T1 maps(dDCE 5min ). To test the dDCE models for shortening the LGE wait time, LGE dDCE images were synthesized using the dDCE 5min maps and compared to the clinical LGE images. Remote and MI dDCE parameters on dDCE 30min and dDCE 5min maps were compared to test the model's ability to extract physiological features. Results: dDCE 30min and dDCE 5min map showed a good visuospatial difference between remote and MI(Fig. 1A) and no quantitative difference (Fig.1B). v e and PS showed a significant elevation in MI than in remote (61.12±13.65% vs 13.43±5.00%, P =0.018; 44.62±21.40mL/g/min vs 0.42±0.55mL/g/min, P =0.018, respectively). v p and F p were significantly decreased in MI than in remote (4.17±2.06% vs 10.85±3.77%, P =0.02; 1.11±0.32mL/g/min vs 1.51±0.42mL/g/min, P =0.04, respectively). Representative LGE and LGE dDCE images showed high agreement in the presence of MI (Fig. 2A). Bland-Altman analysis showed good agreement between LGE and LGE dDCE images for the measurement of infarct area (bias, -1.74 ± 6.60 %, Fig. 2B) and transmuraltiy (bias, 1.86 ± 2.73 %, Fig. 2C). The simple liner regression showed strong correlations between LGE and LGE dDCE images for the infarct area (R 2 , 0.95; slope, 0.93, P &lt;0.01; Fig. 2D) and transmurality (R 2 , 0.97; slope, 0.93, P &lt;0.01; Fig. 2E). ROC analysis showed that the AUC was 0.97 (95% CI: 0.94 to 1.00) (Fig. 2F). Increased lesion-blood pool contrast by 10 folds on dDCE images improved subendocardial MI detection (Fig.3). Conclusions: The developed dDCE model provides comparable viability assessment ability to the standard LGE images without the prolonged wait time and reflects MI pathophysiological changes. It shows the potential for a rapid and quantitative myocardial viability imaging protocol using cardiac magnetic resonance.

Abstract 4136394: Elucidation of a novel genetic substrate responsible for genetically elusive ring-like arrhythmogenic cardiomyopathy

Background: Arrhythmogenic cardiomyopathy (ACM) is a genetic heart disease characterized by fibrofatty replacement of ventricular myocardium. Arrhythmogenic left ventricular (LV) cardiomyopathy (ALVC) is a phenotypic variant of ACM predominantly involving the LV. Mutations in genes encoding for desmosome proteins and filamin C have been implicated in ALVC, especially in the setting of a ring-like late gadolinium enhancement (LGE) imaging pattern. Objective: To identify the underlying genetic substrate responsible for genetically elusive ring-like ALVC in a patient with seemingly sporadic/recessive disease. Methods: A 38-year-old male was referred for genetic investigation to determine the underlying genetic substrate responsible for his ALVC phenotype. The patient fulfilled both electrocardiographic (low voltage in the limb leads and anterolateral T-wave inversions) and imaging (&gt;1 segment of subepicardial LGE) criteria for ALVC. Additionally, the patient experienced unexplained episodes of tachycardia, shakiness, sweating, and nausea prompting concern for an underlying neuromuscular disease. Genome sequencing (GS) was performed on DNA isolated from the affected patient and both of his unaffected parents. Variants were filtered assuming either a sporadic de novo occurrence or an autosomal recessive inheritance pattern. Results: GS identified compound heterozygous GNPTAB variants in the affected patient. A previously reported maternally derived p.Leu257Leu (c.771G&gt;A) variant involving the last nucleotide of exon 7 of the GNPTAB gene and a novel paternally inherited Lys834fs*5 frame-shift variant were identified. The p.Leu257Leu variant has been reported to cause aberrant splicing and exon skipping of the GNPTAB mRNA transcript. Pathogenic variants in the GNPTAB encoded N-acetylglucosamine-1 (GlcNAc)-phosphotransferase subunits alpha/beta cause mucolipidosis type III, a rare recessive lysosomal storage disease characterized by coarse facial features, developmental delay, short stature, skeletal deformities, and cardiac involvement including valvular thickening and cardiomyopathy. Conclusions: Here, using a genome sequencing trio analysis we identified a compound heterozygous GNPTAB pathogenic variants as the underlying genetic substrate in a patient with ring-like ALVC and concomitant neuromuscular disease manifestation. Genome sequencing may identify the genetic etiology responsible for an otherwise undifferentiated diagnosis of cardiomyopathy.

Abstract 4138272: CMR Quantification of Myocardial Oxygenation Extraction Fraction Maps Using a Model-based Self-supervised Learning Network: Initial Experience in Patients with Cardiomyopathies

Background: Measurements of myocardial oxygenation extraction fraction (mOEF) maps with cardiovascular magnetic resonance (CMR) has been recently developed to assess myocardial oxygen metabolism in healthy. Recent studies focus on developing supervised machine learning methods to improve the quantification of mOEF. However, these supervised learning methods may be limited by the lack of ground-truth mOEF maps because MRI cannot directly measure mOEF with the same precision as PET. Hypothesis: Model-based self-supervised learning neural networks maybe feasible to generate mOEF maps accurately. Aims: To develop a physical model-based self-supervised learning neural network to accurately estimate mOEF for the patients with a variety of cardiomyopathies. Methods: An ECG triggered, two-dimensional asymmetric spin-echo (ASE) prepared sequence was employed to scan 71 patients with dilated, hypertrophic, or ischemic cardiomyopathies. At least 3 slices were scanned for each patient and each ASE scan was performed free-breathing with a spatial resolution of 1.7 × 1.7 × 8 mm 3 and scan time of 18 RR-interval. Acquisition of late gadolinium enhancement (LGE) was performed in each patient after the administration of 0.15 mmol/kg gadolinium agent for the visualization of myocardial infarction regions. A fully convolutional neural network with U-Net architecture was optimized with a physical model-based signal loss function (see Figure 1) on the ASE training dataset from 67 patients to generate mOEF maps. To evaluate if the method can accurately quantify abnormal mOEF, four patients with myocardial infarction were selected as the test set. Results: A previous publication reported normal mOEF levels at approximately 0.6-0.7 in healthy subjects. Figure 2 shows our proposed method generated mOEF maps from two representative patients and their LGE images for comparisons. In comparison with the remote region (mOEF = 0.70±0.10), the mOEF of myocardial regions with infarction was significantly lower (mOEF = 0.36±0.12, p &lt; 0.001). The infarction areas predicted by the network overlapped well with the LGE. Conclusion: Quantification of mOEF using the proposed model-based self-supervised U-Net is feasible to detect abnormalities in regional myocardial oxygenation. Current study is ongoing to evaluate the proposed technique in a large cardiac patient dataset.

Magnetic Resonance Myocardial Imaging in Patients With Implantable Cardiac Devices: Challenges, Techniques, and Clinical Applications.

Cardiovascular magnetic resonance imaging (MRI) in patients with cardiac implants, such as pacemakers and defibrillators, has gained importance in recent years with the development of modern cardiac implantable electronic devices. The increasing clinical need to perform MRI examinations in patients with cardiac implants has driven the development of new advanced MRI sequences to mitigate image artifacts associated with cardiac implants. More specifically, advances in imaging techniques, such as wideband late gadolinium enhancement imaging, wideband T1 mapping, and wideband perfusion, have been designed to improve image quality and examinations in patients with cardiac implants, enabling a comprehensive and more reliable diagnosis, which was previously unattainable in these patients. This review article explores recent developments and applications of wideband techniques in the field of cardiovascular MRI, offering insights into their transformative potential. Clinical applications of wideband cardiovascular MRI are highlighted, particularly in assessing myocardial viability, guiding ventricular tachycardia ablation, and characterizing myocardial tissue.

Subclinical myocardial fibrosis is almost ubiquitous in the hearts of older British persons: 'MyoFit46' cardiovascular sub-study of the NSHD

Abstract Background Unprecedented numbers are now surviving to older age, but little is known about the burden or pattern of myocardial fibrosis in the asymptomatic elderly population. Previous 1.5 Tesla (T) cardiovascular magnetic resonance (CMR) studies found a prevalence of unexpected infarct-pattern late gadolinium enhancement (LGE) of 17-20% above 75 years but less is known about non-infarct pattern scar in this group. We investigated the prevalence, patterns, and clinical predictors of left ventricular (LV) scar in a large asymptomatic older age cohort. Methods CMR with a single 3T magnet was performed on participants all born in the same week in March 1946, as part of the longest running continued surveillance birth cohort: the National Survey of Health and Development. LV short-axis stack LGE imaging was performed using a free-breathing motion-corrected balanced steady-state free precession sequence with phase-sensitive inversion-recovery. Two blinded observers independently recorded the prevalence, extent, and pattern of LGE per participant. Logistic regression was used to study the association between clinicodemographic parameters and LGE. Results 460 participants were prospectively recruited of which 406 completed CMR with LGE imaging (77.8 ± 0.1 years, 44% male). 341 (84%) demonstrated LGE affecting a mean of 2.1±1.2 myocardial segments per participant (Figure 1). The commonest pattern of LGE was inferior right ventricular insertion point (RVIP), observed in 66.9%. Other patterns included (Figure 2): Linear mid-wall (19.6%) of which 38% were located in the inferior/lateral walls; subepicardial (12.1%); subendocardial infarct-pattern (8.8%); patchy/diffuse (1.6%); embolic LGE (0.6%). Sub-analysis was performed comparing those without significant unexpected fibrosis (LGE–) vs those with focal fibrosis (LGE+, excluding RVIP and those participants with a known history of prior myocardial infarction). LGE+ participants were more likely to be female (71.7% vs 49.1%, p&amp;lt;0.001) or diabetic (11.3% vs 5.1%, p=0.05), had a higher body surface area (BSA, 1.9 vs 1.8 m2, p&amp;lt;0.001), weight (80.1 vs 72.8 kg, p&amp;lt;0.001), LV indexed end systolic volume (24.2 vs 20.4 ml/m2, p=0.001) and LV indexed mass (59.2 vs 55.4 g/m2, p&amp;lt;0.001), and a lower LV ejection fraction (67.9 vs 71.8%, p&amp;lt;0.001) In multivariable logistic regression: BSA, LV indexed mass, LV ejection fraction and diabetic status were independently associated with LGE+ status (odds ratios [95% confidence intervals]: 9.4 [0.7–3.8]; 1.0 [0.01–0.05]; 0.9 [-0.08--0.02]; and 2.5 [0.03–1.7] respectively, p&amp;lt;0.05). Conclusion Advanced PSIR MOCO LGE imaging at 3T reveals that the majority (84%) of asymptomatic British persons above the age of 75 harbour unexpected ‘subclinical’ focal fibrosis, with a substantial proportion of these scars consistent with probable historical myocarditis events. Further work will now explore the life-course determinants of this scar burden in the older age human heart.

Study design of the CARDIO-TTRansform cardiac magnetic resonance imaging substudy

Abstract Background Cardiac magnetic resonance (CMR) with extracellular volume (ECV) mapping can track treatment response in patients with cardiac amyloidosis by assessing changes in cardiac amyloid burden along with associated changes in structure and function. The CARDIO-TTRansform trial is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial designed to assess the efficacy and safety of eplontersen in transthyretin amyloid cardiomyopathy (ATTR-CM). Eplontersen is a ligand-conjugated antisense oligonucleotide designed to reduce hepatic production of transthyretin protein, the amyloid fibril precursor protein in ATTR-CM. Patients with hereditary or wild-type ATTR-CM on available standard of care were randomized 1:1 to receive 45 mg of eplontersen or placebo via subcutaneous injection every 4 weeks. Patients in the main study with no contraindication to CMR were invited to participate in this sub-study. Purpose The primary objective is to measure the change in amyloid burden (defined as % change in ECV from baseline) over time in patients receiving eplontersen versus placebo. Methods Participants will undergo CMR with ECV mapping at baseline, 25, 49, 97 and 140 weeks (Figure 1). Images will be acquired under a standardized protocol comprising cine imaging with steady state free precession sequence, late gadolinium enhancement imaging (LGE) and T1 mapping. T1 mapping will be performed before the administration of contrast and will be repeated 15 minutes post-contrast using the same slice locations, to produce ECV maps. Results In the main study, 1432 patients were randomized from 120 sites across 20 countries. Of these patients, 157 patients were enrolled in the CMR sub-study, from 6 centers across 4 countries. Images will be read centrally at the end of the study. All participants in the study will also receive serial transthoracic echocardiography with strain analysis to correlate findings with conventional imaging techniques, and a subset of patients from the CMR substudy will be co-enrolled in a scintigraphy substudy for further characterization of amyloid deposition in their heart. Conclusion The CARDIO-TTRansform CMR substudy represents the largest CMR study of ATTR-CM. The CMR sub-study has enrolled a broad global population of patients with hereditary and wild-type ATTR-CM and will provide key information on the impact of eplontersen on the cardiac amyloid load and the associated change in structure and function.

Mechanisms affecting the neutrophil to lymphocyte ratio in heart failure: a prospective CMR study

Abstract Background The neutrophil-to-lymphocyte ratio (NLR) is a simple measure of inflammation defined as the ratio of the neutrophils to lymphocytes as measured in the full blood count. It is well known that patients with heart failure (HF) have elevated levels of pro-inflammatory cytokines. It has been demonstrated in a recent meta-analysis that elevated NLR in heart failure is significantly associated with worse outcomes including all-cause mortality, heart failure readmissions and cardiovascular death. Purpose Given this association between NLR and adverse prognosis in HF, we aim to identify which factors are associated with an elevated NLR. This may help to recognise patients at higher risk and guide management. Methods Patients with newly diagnosed HF and left ventricular ejection fraction &amp;lt;50% on referral echocardiogram were prospectively recruited at the time of referral for cardiovascular magnetic resonance (CMR). Exclusion criteria included prior revascularisation, myocardial infarction, anginal chest pain, congenital heart disease and suspected myocarditis. In one appointment patients (N=599) underwent clinical assessment, medication review, full blood count and CMR. The CMR protocol included quantitative assessment myocardial blood flow at stress and rest, assessment of ischaemic and non-ischaemic fibrosis by late gadolinium enhancement imaging and T1 and T2 mapping. Guideline directed medical therapy was determined by the referring physician. Baseline demographic data, medication and MRI results were recorded for all patients. NLR was calculated from full blood count and split into tertiles. Clinical and CMR parameters were compared between tertiles by analysis of variance and chi squared test. Results See Table 1 The factors which were found to be significantly associated with an elevated NLR were age, atrial fibrillation, NTproBNP, diuretic dose, inducible ischaemia and ischaemic fibrosis. Of note there was no significant difference between groups in terms of guideline directed medical therapy use or other CMR parameters. Conclusion NLR is increasingly recognised as a marker of adverse risk in patients with heart failure. This prospective study of 599 heart failure patients with reduced ejection fraction has identified that an elevated NLR is associated with: 1. Evidence of congestion as evidenced by NTproBNP results and increased diuretic doses. 2. Occult coronary artery disease as shown by greater levels of inducible ischaemia and ischaemic fibrosis. These findings suggest that the adverse prognosis associated with elevated NLR in heart failure may be mediated by worsening congestion and occult coronary artery disease. Importantly there was no association between myocardial inflammation or oedema (measured as native T1 and T2) and NLR. Whether NLR improves with medical therapy of heart failure remains to be established and our findings need to be validated in more varied cohorts of patients with heart failure.

Deep learning for quantification of myocardial scar and microvascular obstruction in late gadolinium enhancement cardiovascular magnetic resonance images

Abstract Objectives Detecting and measuring myocardial scar and microvascular obstruction (MVO) accurately following reperfusion therapy is clinically vital for patients with acute myocardial infarction (AMI). Current clinical practice relies on manual delineation of endocardial borders as well as hyper- and hypo-enhanced regions on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) images for scar and MVO quantification, respectively. However, this approach is subjective, labor-intensive, and time-consuming. The objective of this study is to develop and assess a convolutional neural network (CNN)-based method for the automated quantification of LGE scar and MVO in AMI patients. Methods A total of 1836 LGE images from 252 patients with AMI were analyzed, with the cohort comprising 232 males and an average age of 56±9 years. Our approach, utilizing a combined architecture of cascaded YOLOv8 (You Only Look Once version 8) and nnU-Net, was implemented for the simultaneous segmentation of the left ventricular (LV) myocardium, scar, and MVO in LGE images. Independent datasets for training, validation, and testing were maintained in an 8:1:1 ratio. Performance evaluation was conducted by comparing the results to manual scar and MVO quantification, utilizing metrics such as the Dice similarity coefficient (DSC) and Bland-Altman analysis. Results The automated segmentation process took 0.05 seconds per image. The segmentation accuracy, as assessed by the DSC, yielded values of 0.96±0.04 (per-patient, n=25) and 0.96±0.05 (per-slice, n=184) for scar segmentation, and 0.86±0.17 (per-patient) and 0.89±0.15 (per-slice) for MVO segmentation. In per-patient analysis, the volumes of automatically segmented scar and MVO demonstrated strong agreement with manually derived results, with biases [limits of agreement] of -0.3 [-3.0, 2.4] cm³ and 0.1 [-0.2, 0.3] cm³, respectively. Furthermore, there was strong concordance between automatically and manually derived scar size as a percentage of LV mass (-0.2 [-3.1, 2.7] %) and MVO size as a percentage of scar (1.2 [-5.6, 8.0] %). Conclusions The findings demonstrate excellent agreement between our proposed automated deep-learning solution and clinical expert annotation, suggesting its potential as a predictive tool for prognosis and clinical outcomes in patients with AMI.

Iron chelation therapy failed to improve cardiac dysfunction caused by mitochondrial injury in rats with iron overload cardiomyopathy a 7T Cardiac MR research in vivo

Abstract Purpose To assess the efficacy of iron chelation therapy in improving cardiac function in iron overload cardiomyopathy (IOC) rats by using Cardiac magnetic resonance feature-tracking (CMR-FT). Methods The IOC rat model was induced by intraperitoneal injection of iron dextran over 2 months. Subsequently, 7 rats with IOC were assigned as IOC group to receive continued intraperitoneal injections of saline for an additional 2 months, while another group of 5 rats received intraperitoneal injections of deferoxamine (DFO) for the same duration, forming the IOC+DFO group. Meanwhile, a control group consisting of 7 healthy rats received intraperitoneal injections of saline for the entire duration of 4 months. All rats underwent a 7T CMR scan to assess cardiac function, myocardial iron overload, and myocardial fibrosis via cine, T2 mapping, and late gadolinium enhancement (LGE) scanning, respectively. The cardiac function analysis included left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain (GLS) using cine images. Following CMR scans, all rats underwent open-chest blood collection to detect serum iron levels, and cardiac gross specimens were then subjected to pathological staining, including hematoxylin and eosin (HE) for cardiomyocytes injury, Prussian blue for iron deposition , and Masson staining for myocardial fibrosis. Furthermore, the ultrastructure of cardiomyocyte was examined using transmission electron microscopy (TEM). Results The T2 value, measured in the septum wall at the mid-layer of the LV, and LVEF, and GLS exhibited a significant decrease in the IOC or IOC+DFO group, compared to the control group, while there were no significant difference observed between the IOC and IOC+DFO group (Fig. 1A, B, C). Myocardial fibrosis was not detected in the LGE images in both IOC and IOC+DFO group. Compared to the control group (37.5±12.5μmol/L) , serum iron levels were significantly elevated in the IOC group (368.6±181.0μmol/L) and in chelation treatment group (106.1±32.2μmol/L). Histological examination with HE staining revealed a normal arrangement of myocardial cells in all rats, without cellular degeneration or necrosis. Prussian blue staining highlighted the presence of iron particles within the myocardial interstitium in the IOC and IOC+DFO groups. Masson staining demonstrated intact myocardial muscle bundles without any evidence of myocardial fibrosis. Transmission electron microscopy (TEM) revealed myocardial mitochondria injury, characterized by ruptured outer membranes, reduced cristae, and vacuolization. Conclusions Following iron chelation therapy, the excessive iron burden in the bloodstream was alleviated. However, myocardial iron overload persisted in IOC rats, with no significant improvement in cardiac function observed. This persistence may be attributed to mitochondrial injury. The findings underscore the importance of monitoring cardiac dysfunction in patients with iron overload.CMR parameters analysis in IOC rats

Impaired myocardial energetics in both sarcomere positive and negative HCM are linked to arrhythmic risk

Abstract Background Impaired myocardial energetics play a pivotal role in the complex pathophysiology of hypertrophic cardiomyopathy (HCM), and are thought to be mediated by energy-costly sarcomeric mutations and mitochondrial dysfunction (1). Two thirds of HCM patients, however, do not possess pathogenic sarcomeric mutations (2) and instead develop the condition due to a combination of increased polygenic susceptibility and comorbidities. Whether energetic impairment, a target of novel HCM treatments (e.g., myosin modulators such as Mavacamten), similarly affects sarcomere mutation positive (Sarc+) and negative (Sarc-) HCM remains unclear, as does the association between impaired energetics and markers of arrhythmic risk such as hypertrophy severity, cardiac function and non-sustained ventricular tachycardia (NSVT). This study aimed to investigate differences in resting myocardial energetics between Sarc+ and Sarc- HCM by measuring the phosphocreatine-to-adenosine triphosphate (PCr/ATP) ratio using phosphorus magnetic resonance spectroscopy (31P-MRS) and explore the association between impaired energetics and markers of arrhythmic risk in HCM. Methods We recruited one hundred (100) participants (80 non-obstructive HCM patients and 20 age- and sex-matched controls). Myocardial energetics were assessed using 31P-MRS to measure the PCr/ATP ratio. Cardiac magnetic resonance (CMR) imaging including cine, T1 (ShMOLLI), quantitative pixel-wise perfusion mapping (3) and late gadolinium enhancement (LGE) imaging was also performed. In addition, HCM patients underwent 7-day ECG monitoring to document NSVT episodes (3 beats ≥120 bpm). Results HCM patients had impaired myocardial energetics (PCr/ATP ratio) relative to controls (HCM 1.64±0.36 vs controls 1.97±0.32 p&amp;lt;0.001). PCr/ATP ratios did not differ between Sarc+ and Sarc- HCM even after adjustment for confounders including age, hypertrophy and fibrosis burden (Sarc+ 1.64 [1.50-1.78] vs Sarc- 1.64 [1.52-1.77], p=0.993). PCr/ATP ratio showed no correlation with maximum wall thickness (p=0.257), left ventricular ejection fraction (p=0.727) or myocardial perfusion reserve (p=0.851), but did inversely correlate with global longitudinal strain (r=-0.3, p=0.025). Reduced PCr/ATP was associated with presence of fibrosis (LGE+ 1.58±0.35 vs LGE- 1.79±0.37 p=0.025) and with NSVT, independent of age or fibrosis burden (NSVT+ 1.54 [1.40-1.67] vs NSVT- 1.73 [1.62-1.86], p=0.046). Conclusion Myocardial energetics are similarly impaired in Sarc+ and Sarc- HCM, and are independently associated with impaired contractility, greater fibrosis severity and heightened arrhythmic risk. Our findings provide novel mechanistic insights into the potentially favourable response of HCM patients to energy-sparing myosin modulator therapies irrespective of genotype and highlight the potential for cardiac energetics to serve as a marker of arrhythmic risk.

Assessing myocardial tissue in the acute setting with Photon-Counting CT (PCCT) in comparison with Cardiac Magnetic Resonance (CMR)

Abstract Background Cardiac magnetic resonance (CMR) characterization of myocardial tissue is routinely used in clinical practice. Compared to traditional CT, Photon counting CT (PCCT) uses photon-counting detectors offering higher spatial resolution, elimination of electronic noise and improved contrast-to-noise ratio. A comparison between CMR and PCCT for myocardial characterizazion in an urgent setting, however, has not yet been explored. Purpose The aim of this study was to compare the ability to characterize myocardial tissue between PCCT and CMR in patients presenting with acute chest pain in the emergency department (ED). Methods This single-center prospective study enrolled all consecutive patients presenting to the ED of our hospital from November 2023 to January 2024 with chest pain, ECG alterations and troponin rise consistent with myocardial injury. Patients needing urgent coronary angiography according to guidelines were excluded. PCCT was performed urgently for triple rule-out, but also for tissue characterization through post-iodine-contrast administration images. Within 24 hours, all patients underwent a CMR protocol including T2-weighted and late gadolinium enhancement (LGE) images for tissue characterization. Results Six male patients with a mean age of 20 ± 10 years were enrolled. All clinical, PCCT, and CMR parameters are presented in Table 1. All patients presented with diffuse ST-segment elevation and exhibited T2-weighted images (for edema detection) and LGE distribution (subepicardial and intramyocardial) consistent with acute myocarditis. Mean radiation exposure for PCCT was 0.8±0.1 mSv. A strong linear correlation emerged between PCCT-derived delayed enhancement (DE) volume and CMR-derived late gadolinium enhancement (LGE) volume (r = 0.970; p value 0.001) (Table 1). Similar results were achieved when comparing the number of DE and LGE myocardial segments (r = 0.871; p value 0.026). Significant correlations also emerged between DE, LGE, and high-sensitive troponin (hsTN) at presentation (respectively: PCCT-DE vs hsTN r = 0.951, p value 0.004; CMR-LGE vs hsTN r = 0.918, p value 0.010). CMR showed a much higher signal-to-noise ratio (SNR) for the delayed enhanced myocardium and contrast-to-noise (CNR) ratio between the delayed enhanced and normal myocardium with respect to PCCT in post-contrast images (respectively 7.4 ± 3.9 vs 27.2 ± 17.7, p value 0.024 and 5.5 ± 3.7 vs 38.8 ± 30.2, p value 0.023). In T2-weighted images both SNR for the hyperintense myocardium (30.3 [20.4-122.4]) and CNR between the hyperintense and normal myocardium (26.7 [13.3-60.2]) resulted to be higher compared to PCCT (p value 0.027 and 0.045, respectively) (Table 1). Conclusions PCCT appears to be reliable when compared to CMR for detecting myocardial edema through the acquisition of post-contrast images in the acute setting with an acceptable CNR.

Quantitative molecular imaging of cardiac fibrosis and response to treatment using a novel collagen III-specific MR imaging probe

Abstract Background Heart failure (HF) remains a major cause of morbidity and death affecting 64 million people globally[1]. Myocardial fibrosis, characterised by changes in type I (COL1) and III (COL3) collagen levels, may lead to HF [2,3]. Cardiac magnetic resonance (CMR) is a preferred method to detect fibrosis non-invasively, however it provides only indirect measures of fibrosis. Molecular imaging can directly visualise fibrosis, but current imaging probes target COL1. Purpose Here, we developed a COL3-specific probe and used molecular CMR imaging to directly quantify, previously undetectable, COL3 remodelling following myocardial infarction and to monitor treatment response. Methods Myocardial infarction (MI) was induced in mice by permanent ligation of the left anterior descending artery (LAD). Functional and molecular CMR images were acquired at days 10 and 21 post-MI in untreated and mice treated with Enalapril (20mg/kg/day) (n=6/group) using a 3T clinical MRI scanner. A subgroup of untreated mice was also imaged using a negative control probe and Gadovist (n=3). Cardiac function was assessed using 2D short-axis cine images of the left ventricle, and late gadolinium enhancement (LGE) images were obtained using T1-weighted 3D inversion recovery (IR) imaging. T1 mapping was performed using a 2D Look-Locker sequence with thirty inversion recovery images. Results Molecular CMR enabled selective profiling of the natural turnover of COL3 after MI with strong signal enhancement at day 10, and decreased enhancement at day 21 when COL3 is replaced by COL1 (Fig. 1A). Quantitative T1 maps discriminated between infarcted and remote myocardium with lower T1 values in the infarct and higher in the remote myocardium. Importantly, there was no enhancement using the scrambled probe or the clinical agent Gadovist. The imaging data were validated by histology (Fig.1B). Mice treated with Enalapril showed similar enhancement at day 10 compared to untreated mice (Fig. 2A). However, at day 21 mice treated with Enalapril showed higher signal enhancement compared to untreated mice, suggesting that Enalapril may prolong the presence of COL3 in the infarcted myocardium. Quantification of signal enhancement showed the increase in LGE volume and R1 relaxation rates within the infarcted myocardium at day 10, the subsequent decrease at day 21 and the prolongation of the COL3 signal at day 21 in enalapril treated mice (Fig.2B-C) Despite changes in cardiac fibrosis detected with molecular imaging, cardiac function was similar between the groups (Fig. 2D), suggesting that molecular change may precede functional changes. Conclusion(s) Quantitative molecular CMR imaging of COL3 enabled visualisation of changes in COL3 after MI and in response to treatment for the first time. This approach may provide insights into the role of COL3 in cardiac fibrosis and provide an non-invasive method to detect fibrosis early, stage fibrosis and monitor therapeutic response.