Deep learning for automatic volumetric segmentation of left ventricular myocardium and ischaemic scar from multi-slice late gadolinium enhancement cardiovascular magnetic resonance.

AIMS: This study details application of deep learning for automatic volumetric segmentation of left ventricular (LV) myocardium and scar and automated quantification of myocardial ischaemic scar burden from late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR). METHODS AND RESULTS: We included 501 images and manual segmentations of short-axis LGE-CMR from over 20 multinational sites, from which 377 studies were used for training and 124 studies from unique participants for internal validation. A third test set of 52 images was used for external evaluation. Three models, U-Net, Cascaded U-Net, and U-Net++, were trained with a novel adaptive weighted categorical cross-entropy loss function. Model performance was evaluated using concordance correlation coefficients (CCCs) for LV mass and per cent myocardial scar burden. Cascaded U-Net was found to be the best model for the quantification of LV mass and scar percentage. The model exhibited a mean difference of -5 ± 23 g for LV mass, -0.4 ± 11.2 g for scar mass, and -0.8 ± 7% for per cent scar. CCC were 0.87, 0.77, and 0.78 for LV mass, scar mass, and per cent scar burden, respectively, in the internal validation set and 0.75, 0.71, and 0.69, respectively, in the external test set. For segmental scar mass, CCC was 0.74 for apical scar, 0.91 for mid-ventricular scar, and 0.73 for basal scar, demonstrating moderate to strong agreement. CONCLUSION: We successfully trained a convolutional neural network for volumetric segmentation and analysis of LV scar burden from LGE-CMR images in a large, multinational cohort of participants with ischaemic scar.

The impact of the atrial wall thickness in normal/mild late-gadolinium enhancement areas on atrial fibrillation rotors in persistent atrial fibrillation patients.

Background: Some of atrial fibrillation (AF) drivers are found in normal/mild late-gadolinium enhancement (LGE) areas, as well as moderate ones. The atrial wall thickness (AWT) has been reported to be important as a possible AF substrate. However, the AWT and degree of LGEs as an AF substrate has not been fully validated in humans. Objective: The purpose of this study was to evaluate the impact of the AWT in normal/mild LGE areas on AF drivers. Methods: A total of 287 segments in 15 persistent AF patients were assessed. AF drivers were defined as non-passively activated areas (NPAs), where rotational activation was frequently observed, and were detected by the novel real-time phase mapping (ExTRa Mapping), mild LGE areas were defined as areas with a volume ratio of the enhancement voxel of 0% to <10%. The AWT was defined as the minimum distance from the manually determined endocardium to the epicardial border on the LGE-MRI. Results: NPAs were found in 20 (18.0%) of 131 normal/mild LGE areas where AWT was significantly thicker than that in the passively activated areas (PAs) (2.5 ± 0.3 vs. 2.2 ± 0.3 mm, p < .001). However, NPAs were found in 41 (26.3%) of 156 moderate LGE areas where AWT was thinner than that of PAs (2.1 ± 0.2 mm vs. 2.23 ± 0.3 mm, p = .02). An ROC curve analysis yielded an optimal cutoff value of 2.2 mm for predicting the presence of an NPA in normal/mild LGE areas. Conclusion: The location of AF drivers in normal/mild LGE areas might be more accurately identified by evaluating AWT.

Comparison of various late gadolinium enhancement magnetic resonance imaging methods with high-definition voltage and activation mapping for detection of atrial cardiomyopathy.

AIMS: Atrial cardiomyopathy (ACM) is associated with increased arrhythmia recurrence rates after pulmonary vein isolation (PVI). We compare the most common left atrial (LA) late gadolinium enhancement magnetic resonance imaging (LGE-MRI)-methods [Utah-method and image intensity ratio (IIR)-methods] and endocardial voltage mapping for ACM-detection and outcome prediction after PVI for atrial fibrillation (AF). METHODS AND RESULTS: In this prospective observational study, 37 ablation-naive patients (66 ± 9 years, 84% male) with persistent AF underwent LA-LGE-MRI and high-definition voltage and activation mapping (2129 ± 484 sites) in sinus rhythm prior to PVI. The MRI-post-processing-analyses were performed by two independent expert laboratories. Arrhythmia recurrence was recorded within 12 months following PVI. The global ACM-extent was highly variable: median LA low-voltage substrate (LA-LVS) was 12.9% at <1.0 mV and 2.7% at <0.5 mV; median LA-LGE-extent using the Utah-method was 18.3% and 0.03-93.1% using the IIR-methods. The LA activation time was significantly correlated with LA-LVS (r = 0.76 at <0.5 mV and r = 0.82 at <1.0 mV, both P < 0.0001), but not with LA-LGE-extent. The highest regional matching between LA-LVS <0.5 mV and LA-LGE was found for the anterior wall in 57% of patients using the Utah-method and in 59% using IIR 1.20. The corresponding values for the posterior wall were 19% and 38%, respectively. Arrhythmia recurrence occurred in 15(41%) patients. Freedom from arrhythmia was significantly lower in those with LA-LVS ≥2 cm2 at 0.5 mV but not in those with LGE ≥20% (Utah-stages III and IV): 43% vs. 81%, P = 0.009 and 50% vs. 67%, P = 0.338, respectively. CONCLUSION: Comparison of the most common LA-LGE-MRI methods and endocardial voltage mapping revealed large discrepancies in global and regional ACM-extent.

Evaluation of combined late gadolinium-enhancement and functional cardiac magnetic resonance imaging using spiral real-time acquisition.

The purpose of the current study was to implement and validate joint real-time acquisition of functional and late gadolinium-enhancement (LGE) cardiac magnetic resonance (MR) images during free breathing. Inversion recovery cardiac real-time images with a temporal resolution of 50 ms were acquired using a spiral trajectory (IR-CRISPI) with a pre-emphasis based on the gradient system transfer function during free breathing. Functional and LGE cardiac MR images were reconstructed using a low-rank plus sparse model. Late gadolinium-enhancement appearance, image quality, and functional parameters of IR-CRISPI were compared with clinical standard balanced steady-state free precession breath-hold techniques in 10 patients. The acquisition of IR-CRISPI in free breathing of the entire left ventricle took 97 s on average. Bland-Altman analysis and Wilcoxon tests showed a higher artifact level for the breath-hold technique (p = 0.003), especially for arrhythmic patients or patients with dyspnea, but an increased noise level for IR-CRISPI of the LGE images (p = 0.01). The estimated transmural extent of the enhancement differed by not more than 25% and did not show a significant bias between the techniques (p = 0.50). The ascertained functional parameters were similar for the breath-hold technique and IR-CRISPI, that is, with a minor, nonsignificant (p = 0.16) mean difference of the ejection fraction of 2.3% and a 95% confidence interval from -4.8% to 9.4%. IR-CRISPI enables joint functional and LGE imaging in free breathing with good image quality but distinctly shorter scan times in comparison with breath-hold techniques.

Successful catheter ablation of postoperative atrial tachycardia with conduction disturbances: Assessment by late-gadolinium enhancement magnetic resonance imaging and high-resolution electro-anatomical mapping.

Atrial tachycardia (AT) in the right atrium often occurs following open-heart surgery. Catheter ablation for these AT is challenging and can lead to unintended conduction block. We performed late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) prior to catheter ablation and predicted wavefront propagation during SR as well as the slow conduction zone during tachycardia. LGE-MRI may assist predicting the conduction disturbance and reducing the risk of unexpected sinus exit block.

Late-gadolinium enhancement properties associated with atrial fibrillation rotors in patients with persistent atrial fibrillation.

BACKGROUND: A computational model demonstrated that atrial fibrillation (AF) rotors could be distributed in patchy late-gadolinium enhancement (LGE) areas and play an important role in AF drivers. However, this was not validated in humans. OBJECTIVE: The purpose of this study was to evaluate the LGE properties of AF rotors in patients with persistent AF. METHODS: A total of 287 segments in 15 patients with persistent AF (long-standing persistent AF in 9 patients) that underwent AF ablation were assessed. Non-passively activated areas (NPAs), where rotational activation (AF rotor) was frequently observed, were detected by the novel real-time phase mapping (ExTRa Mapping). The properties of the LGE areas were assessed using the LGE heterogeneity and the density which was evaluated by the entropy (LGE-entropy) and the volume ratio of the enhancement voxel (LGE-volume ratio), respectively. RESULTS: NPAs were found in 61 (21%) of 287 segments and were mostly found around the pulmonary vein antrum. A receiver operating characteristic curve analysis yielded an optimal cutoff value of 5.7% and 10% for the LGE-entropy and LGE-volume ratio, respectively. The incidence of NPAs was significantly higher at segments with an LGE-entropy of >5.7 and LGE-volume ratio of >10% than at the other segments (38 [30%] of 126 vs. 23 [14%] of 161 segments; p = .001). No NPAs were found at segments with an LGE-volume ratio of >50% regardless of the LGE-entropy. Of five patients with AF recurrence, NPAs outside the PV antrum were not ablated in three patients and the remaining NPAs were ablated, but their LGE-entropy and LGE-volume ratio were low. CONCLUSION: AF rotors are mostly distributed in relatively weak and much more heterogenous LGE areas.

Circulating intermediate monocytes and atrial structural remodeling associated with atrial fibrillation recurrence after catheter ablation.

BACKGROUND: Inflammation, such as that associated with intermediate CD14++ CD16+ monocytes and atrial structural remodeling (SRM), may be important in the recurrence of atrial fibrillation (AF) after catheter ablation. However, the relationship between the intermediate CD14++ CD16+ monocytes, SRM, and AF recurrence is unclear. METHODS: Twenty-four patients with AF were enrolled. The proportion of intermediate monocytes (PIM) was assessed before ablation by flow cytometry. As a surrogate marker of SRM, the volume ratio (VR) of signal intensity greater than 1 standard deviation on late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) was calculated. We investigated whether PIM correlated with SRM on LGE-MRI and determined the optimal cutoff value for predicting AF recurrence. RESULTS: Univariate analysis revealed positive correlations between PIM and BNP with SRM (PIM: r = .593, p = .002; BNP: r = .567, p = .004). Multivariable analysis revealed that PIM was independently associated with VR on LGE-MRI (ß = .522; p = .033). The finding of an area under the receiver operating characteristic curve of 0.750 revealed that a VR ≥ 13.3% on LGE-MRI as the optimal cutoff value to predict AF recurrence with 80% sensitivity and 71% specificity, which was associated with PIM ≥ 10.0%. CONCLUSION: Intermediate monocytes were significantly positively correlated with SRM. PIM ≥ 10% was associated with a VR ≥ 13.3% on LGE-MRI, which predicted AF recurrence after catheter ablation.

Thrombus or vegetation?Importance of cardiac MRI as a diagnostic tool based on case report and literature review.

INTRODUCTION: We report the Case of a 35 years old male patient admitted for pulmonary embolism in a febrile context. Transthoracic echocardiography showed a filamentary mass appended to the pulmonary valve whose thrombotic origin has been suggested on data of late gadolinium enhancement magnetic resonance imaging. CASE PRESENTATION: The patient had a history of deep vein thrombosis in the context of familial thrombophilia with factor V leiden gene mutation in two of his sisters and an inhaled drug addiction to heroïn. There was a biological inflammatory syndrome with negative blood cultures. Transthoracic echocardiography showed a very mobile homogeneous hyperechoic mass measuring 8 cm in the right ventricle appended between the pulmonary valve and the lateral wall of the RV. In LGE-MRI, an isointense, to the myocardium, marginal hall and a central rim enhancement were objectified, suggesting the diagnosis of thrombus rather than vegetation. CONCLUSION: Despite the notion of drug addiction, the febrile context and the localization of the mass, a diagnosis of RV thrombus rather than infective endocarditis was favored relying on familial thrompbophilia, personal history of DVT and LGE-MRI aspect. The patient was treated with curative heparin therapy and antibiotic therapy. Due to the persistence of the mass after three weeks of treatment and after heart-team discussion, the patient underwent surgical mass removal. The anatomopathological study confirmed a fibrino-cruoric thrombus.

Correlation of magnetic resonance imaging and post-ablation endoscopy to detect oesophageal thermal injury in patients after atrial fibrillation ablation: MRI-EDEL-study.

AIMS: To correlate oesophageal magnetic resonance imaging (MRI) abnormalities with ablation-induced oesophageal injury detected in endoscopy. METHODS AND RESULTS: Ablation-naïve patients with atrial fibrillation (AF), who underwent ablation using a contact force sensing irrigated radiofrequency ablation catheter, received a cardiac MRI on the day of ablation, and post-ablation oesophageal endoscopy (OE) 1 day after ablation. Two MRI expert readers recorded presence of abnormal oesophageal tissue signal intensities, defined as increased oesophageal signal in T2-fat-saturated (T2fs), short-tau inversion-recovery (STIR), or late gadolinium enhancement (LGE) sequences. Oesophageal endoscopy was performed by experienced operators. Finally, we correlated the presence of any affection with endoscopically detected oesophageal thermal lesions (EDEL). Among 50 consecutive patients (age 67 ± 7 years, 60% male), who received post-ablation MRI and OE, complete MRI data were available in 44 of 50 (88%) patients. In OE, 7 of 50 (14%) presented with EDEL (Category 1 lesion: erosion n = 3, Category 2 lesion: ulcer n = 4). Among those with EDEL, 6 of 7 (86%) patients presented with increased signal intensities in all three MRI sequences, while only 2 of 37 (5%) showed hyperintensities in all three MRI sequences and negative endoscopy. Correspondingly, sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for MRI (increased signal in T2fs, STIR, and LGE) were 86%, 95%, 75%, and 97%, respectively. CONCLUSION: Increased signal intensity in T2fs, STIR, and LGE represents independent markers of EDEL. In particular, the combination of all three has the highest diagnostic value. Hence, MRI may represent an accurate, non-invasive method to exclude acute oesophageal injury after AF ablation (NPV: 97%).

Fully automated segmentation of left ventricular scar from 3D late gadolinium enhancement magnetic resonance imaging using a cascaded multi-planar U-Net (CMPU-Net).

PURPOSE: Three-dimensional (3D) late gadolinium enhancement magnetic resonance (LGE-MR) imaging enables the quantification of myocardial scar at high resolution with unprecedented volumetric visualization. Automated segmentation of myocardial scar is critical for the potential clinical translation of this technique given the number of tomographic images acquired. METHODS: In this paper, we describe the development of cascaded multi-planar U-Net (CMPU-Net) to efficiently segment the boundary of the left ventricle (LV) myocardium and scar from 3D LGE-MR images. In this approach, two subnets, each containing three U-Nets, were cascaded to first segment the LV myocardium and then segment the scar within the presegmented LV myocardium. The U-Nets were trained separately using two-dimensional (2D) slices extracted from axial, sagittal, and coronal slices of 3D LGE-MR images. We used 3D LGE-MR images from 34 subjects with chronic ischemic cardiomyopathy. The U-Nets were trained using 8430 slices, extracted in three orthogonal directions from 18 images. In the testing phase, the outputs of U-Nets of each subnet were combined using the majority voting system for final label prediction of each voxel in the image. The developed method was tested for accuracy by comparing its results to manual segmentations of LV myocardium and LV scar from 7250 slices extracted from 16 3D LGE-MR images. Our method was also compared to numerous alternative methods based on machine learning, energy minimization, and intensity-thresholds. RESULTS: Our algorithm reported a mean dice similarity coefficient (DSC), absolute volume difference (AVD), and Hausdorff distance (HD) of 85.14% ± 3.36%, 43.72 ± 27.18 cm3 , and 19.21 ± 4.74 mm for determining the boundaries of LV myocardium from LGE-MR images. Our method also yielded a mean DSC, AVD, and HD of 88.61% ± 2.54%, 9.33 ± 7.24 cm3 , and 17.04 ± 9.93 mm for LV scar segmentation on the unobserved test dataset. Our method significantly outperformed the alternative techniques in segmentation accuracy (P < 0.05). CONCLUSIONS: The CMPU-Net method provided fully automated segmentation of LV scar from 3D LGE-MR images and outperformed the alternative techniques.

Successful modulation of atrial fibrillation drivers anchoring to fibrotic tissue after box isolation using an online real-time phase mapping system: ExTRa Mapping.

A 41-year-old man with persistent atrial fibrillation (AF) underwent radiofrequency (RF) catheter ablation using an online real-time phase mapping system: ExTRa Mapping. Box isolation could not terminate AF. Subsequently, RF applications on nonpassively activated areas (NPAs), where rotational activations were frequently observed, at the posterior bottom of left atrium outside of box lesion could convert AF to common atrial flutter. Of interest, the NPA near the posterior bottom were located on the patchy fibrotic tissue area assessed by the late-gadolinium enhancement magnetic resonance imaging. This indicated the possibility of the critical AF rotor meandering through the fibrotic tissue area.

Left atrial imaging and registration of fibrosis with conduction voltages using LGE-MRI and electroanatomical mapping.

BACKGROUND AND PURPOSE: Abnormal electrical conduction and excitability associated with fibrosis in the left atrium (LA) may serve as a substrate for atrial fibrillation (AF). Electroanatomical voltage mapping systems (EAMs) have become a dominant facilitator to treat AF with catheter ablation assisted by additional diagnostic imaging modalities. Importantly, AF has been associated with structural changes to the extracellular matrix of the myocardium, including increased collagen deposition-a process known as fibrosis. Late gadolinium enhancement-magnetic resonance imaging (LGE-MRI) may aid in guiding AF cardiac ablation therapy by determination of location of fibrosis in the LA. To locate fibrosis for cardiac ablation, however, accurate registration between EAMs and LGE-MRI data is crucial. The purpose of this work was to develop a method for registering EAMs with late gadolinium enhancement-magnetic resonance (LGE-MR) images of fibrosis. METHODS: Twenty patients with persistent AF, who underwent magnetic resonance imaging scanning and EAMs prior to first-time catheter ablation, participated in the study. In our registration pipeline, LGE-MR images were registered to the left atrial surface on EAMs using manual alignment followed by iterative closest point (ICP), and non-rigid ICP (NICP) algorithm. RESULTS AND CONCLUSIONS: The results demonstrate that NICP provided a substantial reduction in registration error when compared to the use of affine ICP alone. Regions of fibrosis on LGE-MR images identified using the signal threshold to reference mean threshold demonstrated the most regional overlap with low bipolar voltage points on EAMs. Successful co-registration of LGE-MR images to EAMs may assist electro-physiologists in selecting candidate targets for ablation and ultimately, reduce the rate of AF recurrence for patients.

Feasibility of late gadolinium enhancement magnetic resonance imaging to detect ablation lesion gaps in patients undergoing cryoballoon ablation of paroxysmal atrial fibrillation.

BACKGROUND: Although late gadolinium enhancement magnetic resonance imaging (LGE-MRI) allows the identification of lesions and gaps after a cryothermal balloon (CB) ablation of paroxysmal atrial fibrillation (PAF), the accuracy has not yet been well established. METHODS: The subjects consisted of 10 consecutive patients who underwent a second ablation procedure among our cohort of 80 patients who underwent LGE-MRI after the CB ablation of PAF. LGE-MRI scar regions were compared with electroanatomical mapping during the second procedure. In the analysis, the unilateral pulmonary vein (PV) antrum was divided into 7 regions. RESULTS: The gap characterization analysis was performed in 140 regions around 40 PVs in total. There were 16 LGE-MRI gaps around 11 PVs (mean 1.6 ± 1.4 gaps/patient) in 7 patients and 14 electrical gaps around 10 PVs in 8 patients (mean 1.4 ± 1.1 gaps/patient). The locations of 13 electrical gaps were well matched to that on the LGE-MRI, whereas the remaining 1 electrical gap had not been predicted on the LGE-MRI. Compared to the electrical gaps in the second procedure, the sensitivity and specificity of the LGE-MRI gaps were 93% (13 LGE-MRI gaps of 14 electrical gaps) and 98% (123 LGE-MRI scars out of 126 electrical scars), respectively. CONCLUSION: LGE-MRI can accurately localize the lesion gaps after CB ablation of PAF.

Convolutional neural network-based approach for segmentation of left ventricle myocardial scar from 3D late gadolinium enhancement MR images.

PURPOSE: Accurate three-dimensional (3D) segmentation of myocardial replacement fibrosis (i.e., scar) is emerging as a potentially valuable tool for risk stratification and procedural planning in patients with ischemic cardiomyopathy. The main purpose of this study was to develop a semiautomated method using a 3D convolutional neural network (CNN)-based for the segmentation of left ventricle (LV) myocardial scar from 3D late gadolinium enhancement magnetic resonance (LGE-MR) images. METHODS: Our proposed CNN is built upon several convolutional and pooling layers aimed at choosing appropriate features from LGE-MR images to distinguish between myocardial scar and healthy tissues of the left ventricle. In contrast to previous methods that consider image intensity as the sole feature, CNN-based algorithms have the potential to improve the accuracy of scar segmentation through the creation of unconventional features that separate scar from normal myocardium in the feature space. The first step of our pipeline was to manually delineate the left ventricular myocardium, which was used as the region of interest for scar segmentation. Our developed algorithm was trained using 265,220 volume patches extracted from ten 3D LGE-MR images, then was validated on 450,454 patches from a testing dataset of 24 3D LGE-MR images, all obtained from patients with chronic myocardial infarction. We evaluated our method in the context of several alternative methods by comparing algorithm-generated segmentations to manual delineations performed by experts. RESULTS: Our CNN-based method reported an average Dice similarity coefficient (DSC) and Jaccard Index (JI) of 93.63% ± 2.6% and 88.13% ± 4.70%. In comparison to several previous methods, including K-nearest neighbor (KNN), hierarchical max flow (HMF), full width at half maximum (FWHM), and signal threshold to reference mean (STRM), the developed algorithm reported significantly higher accuracy for DSC with a P-value less than 0.0001. CONCLUSIONS: Our experimental results demonstrated that our CNN-based proposed method yielded the highest accuracy of all contemporary LV myocardial scar segmentation methodologies, inclusive of the most widely used signal intensity-based methods, such as FWHM and STRM. To our knowledge, this is the first description of LV myocardial scar tissue segmentation from 3D LGE-MR images using a CNN-based method.

[Structural and Functional Properties of the Left Atrium in Healthy Volunteers and Patients With Atrial Fibrillation: Data of Magnetic Resonance Imaging].

BACKGROUND: in the recent years, there has been an increasing number of publications postulating that data on left atrial (LA) structure obtained by late gadolinium enhancement magnetic resonance imaging (LGE MRI) can improve the management of patients with atrial fibrillation (AF). At the same time, similar data regarding healthy LA myocardium is limited. AIM: to assess structural and functional properties of LA in healthy volunteers (HV) using cardiac magnetic resonance (CMR) (including LGE MRI); to compare these properties in patients with AF and HV. MATERIALS AND METHODS: We included in this study 53 patients with AF (28 without signs of cardiovascular disease, 28 with hypertension) and 23 HV of similar age. All enrolled persons underwent MRI. Cine-MRI was used to assess end diastolic volume of LA (LA EDV), LA ejection fraction (LA EF), left ventricular diastolic index (LV DI). High resolution LGE MRI was performed 15-20 min after gadoversetamide injection using IR 3D gradient echo pulse sequence with fat saturation (TI 290-340 ms, TE 2.44 ms, TR 610-1100ms). On obtained images LA was segmented semiautomatically. LA fibrosis quantification was performed using developed software LGE Heart Analyzer. The extent of fibrosis was represented as percent of LA myocardium volume. Fibrosis location was determined on reconstructed rotating 3D LA model. RESULTS: Compared with patients HV had lower LA EDV (59 [54; 78] ml and 79 [65.5; 86.6] ml, р=0.043, respectively), higher LA EF (56.1 [49; 63.2] % and 44.5 [34.5, 54.5] %, р=0.03, respectively), and lower extent of LA fibrosis (0.7 [0.05; 3.5] % and 9.1 [1.7; 18] %, р.

Optical projection tomography permits efficient assessment of infarct volume in the murine heart postmyocardial infarction.

The extent of infarct injury is a key determinant of structural and functional remodeling following myocardial infarction (MI). Infarct volume in experimental models of MI can be determined accurately by in vivo magnetic resonance imaging (MRI), but this is costly and not widely available. Experimental studies therefore commonly assess injury by histological analysis of sections sampled from the infarcted heart, an approach that is labor intensive, can be subjective, and does not fully assess the extent of injury. The present study aimed to assess the suitability of optical projection tomography (OPT) for identification of injured myocardium and for accurate and efficient assessment of infarct volume. Intact, perfusion-fixed, optically cleared hearts, collected from mice 7 days after induction of MI by coronary artery occlusion, were scanned by a tomograph for autofluorescence emission after UV excitation, generating >400 transaxial sections for reconstruction. Differential autofluorescence permitted discrimination between viable and injured myocardium and highlighted the heterogeneity within the infarct zone. Two-dimensional infarct areas derived from OPT imaging and Masson's trichrome staining of slices from the same heart were highly correlated (r(2) = 0.99, P < 0.0001). Infarct volume derived from reconstructed OPT sections correlated with volume derived from in vivo late gadolinium enhancement MRI (r(2) = 0.7608, P < 0.005). Tissue processing for OPT did not compromise subsequent immunohistochemical detection of endothelial cell and inflammatory cell markers. OPT is thus a nondestructive, efficient, and accurate approach for routine in vitro assessment of murine myocardial infarct volume.

Electroanatomic mapping and late gadolinium enhancement MRI in a genetic model of arrhythmogenic atrial cardiomyopathy.

INTRODUCTION: Although atrial arrhythmias may have genetic causes, very few data are available on evaluation of the arrhythmic substrate in genetic atrial diseases in humans. In this study, we evaluate the nature and evolution of the atrial arrhythmic substrate in a genetic atrial cardiomyopathy. METHODS AND RESULTS: Repeated electroanatomic mapping and tomographic evaluations were used to investigate the evolving arrhythmic substrate in 5 patients with isolated arrhythmogenic atrial cardiomyopathy, caused by Natriuretic Peptide Precursor A (NPPA) gene mutation. Atrial fibrosis was assessed using late gadolinium enhancement magnetic resonance imaging (LGE-MRI). The substrate of atrial tachycardia (AT) and atrial fibrillation (AF) was biatrial dilatation with patchy areas of low voltage and atrial wall scarring (in the right atrium: 68.5% ± 6.0% and 22.2% ± 10.2%, respectively). The evolution of the arrhythmic patterns to sinus node disease with atrial standstill (AS) was associated with giant atria with extensive low voltage and atrial scarring areas (in the right atrium: 99.5% ± 0.7% and 57.5% ± 33.2%, respectively). LGE-MRI-proven biatrial fibrosis (Utah stage IV) was associated with AS. Atrial conduction was slow and heterogeneous, with lines of conduction blocks. The progressive extension and spatial distribution of the scarring/fibrosis were strictly associated with the different types of arrhythmias. CONCLUSION: The evolution of the amount and distribution of atrial scarring/fibrosis constitutes the structural substrate for the different types of atrial arrhythmias in a pure genetic model of arrhythmogenic atrial cardiomyopathy.