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Objectives: We investigate the possibility to exploit high-field MRI to acquire 3D images of Purkinje network which plays a crucial role in cardiac function. Since Purkinje fibers (PF) have a distinct cellular structure and are surrounded by connective tissue, we investigated conventional contrast mechanisms along with the magnetization transfer (MT) imaging technique to improve image contrast between ventricular structures of differing macromolecular content., Methods: Three fixed porcine ventricular samples were used with free-running PFs on the endocardium. T1, T2*, T2, and M0 were evaluated on 2D slices for each sample at 9.4 T. MT parameters were optimized using hard pulses with different amplitudes, offset frequencies and durations. The cardiac structure was assessed through 2D and 3D T1w images with isotropic resolutions of 150 µm. Histology, immunofluorescence, and qPCR were performed to analyze collagen contents of cardiac tissue and PF., Results: An MT preparation module of 350 ms duration inserted into the sequence with a B1 = 10 µT and frequency offset = 3000 Hz showed the best contrast, approximately 0.4 between PFs and myocardium. Magnetization transfer ratio (MTR) appeared higher in the cardiac tissue (MTR = 44.7 ± 3.5%) than in the PFs (MTR = 25.2 ± 6.3%)., Discussion: MT significantly improves contrast between PFs and ventricular myocardium and appears promising for imaging the 3D architecture of the Purkinje network., (© 2021. The Author(s).)

Objectives: This study sought to assess the relationship between fibrosis and re-entrant activity in persistent atrial fibrillation (AF)., Background: The mechanisms involved in sustaining re-entrant activity during AF are poorly understood., Methods: Forty-one patients with persistent AF (age 56 ± 12 years; 6 women) were evaluated. High-resolution electrocardiographic imaging (ECGI) was performed during AF by using a 252-chest electrode array, and phase mapping was applied to locate re-entrant activity. Sites of high re-entrant activity were defined as re-entrant regions. Late gadolinium-enhanced (LGE) cardiac magnetic resonance (CMR) was performed at 1.25 × 1.25 × 2.5 mm resolution to characterize atrial fibrosis and measure atrial volumes. The relationship between LGE burden and the number of re-entrant regions was analyzed. Local LGE density was computed and characterized at re-entrant sites. All patients underwent catheter ablation targeting re-entrant regions, the procedural endpoint being AF termination. Clinical, CMR, and ECGI predictors of acute procedural success were then analyzed., Results: Left atrial (LA) LGE burden was 22.1 ± 5.9% of the wall, and LA volume was 74 ± 21 ml/m 2 . The number of re-entrant regions was 4.3 ± 1.7 per patient. LA LGE imaging was significantly associated with the number of re-entrant regions (R = 0.52, p = 0.001), LA volume (R = 0.62, p < 0.0001), and AF duration (R = 0.54, p = 0.0007). Regional analysis demonstrated a clustering of re-entrant activity at LGE borders. Areas with high re-entrant activity showed higher local LGE density as compared with the remaining atrial areas (p < 0.0001). Failure to achieve AF termination during ablation was associated with higher LA LGE burden (p < 0.001), higher number of re-entrant regions (p < 0.001), and longer AF duration (p = 0.008)., Conclusions: The number of re-entrant regions during AF relates to the extent of LGE on CMR, with the location of these regions clustering to LGE areas. These characteristics affect procedural outcomes of ablation.

To provide a model close to the human heart, and to study intrinsic cardiac function at the same time as electromechanical coupling, we developed a magnetic resonance (MR)-compatible setup of isolated working perfused pig hearts. Hearts from pigs (40 kg, n = 20) and sheep (n = 1) were blood perfused ex vivo in the working mode with and without loaded right ventricle (RV), for 80 min. Cardiac function was assessed by measuring left intraventricular pressure and left ventricular (LV) ejection fraction (LVEF), aortic and mitral valve dynamics, and native T1 mapping with MR imaging (1.5 Tesla). Potential myocardial alterations were assessed at the end of ex vivo perfusion from late-Gadolinium enhancement T1 mapping. The ex vivo cardiac function was stable across the 80 min of perfusion. Aortic flow and LV-dP/dtmin were significantly higher (P < 0.05) in hearts perfused with loaded RV, without differences for heart rate, maximal and minimal LV pressure, LV-dP/dtmax, LVEF, and kinetics of aortic and mitral valves. T1 mapping analysis showed a spatially homogeneous distribution over the LV. Simultaneous recording of hemodynamics, LVEF, and local cardiac electrophysiological signals were then successfully performed at baseline and during electrical pacing protocols without inducing alteration of MR images. Finally, (31)P nuclear MR spectroscopy (9.4 T) was also performed in two pig hearts, showing phosphocreatine-to-ATP ratio in accordance with data previously reported in vivo. We demonstrate the feasibility to perfuse isolated pig hearts in the working mode, inside an MR environment, allowing simultaneous assessment of cardiac structure, mechanics, and electrophysiology, illustrating examples of potential applications., (Copyright © 2016 the American Physiological Society.)

Background: Cardiovascular magnetic resonance (CMR) can through the two methods 3D FLASH and diffusion tensor imaging (DTI) give complementary information on the local orientations of cardiomyocytes and their laminar arrays., Methods: Eight explanted rat hearts were perfused with Gd-DTPA contrast agent and fixative and imaged in a 9.4T magnet by two types of acquisition: 3D fast low angle shot (FLASH) imaging, voxels 50 × 50 × 50 μm, and 3D spin echo DTI with monopolar diffusion gradients of 3.6 ms duration at 11.5 ms separation, voxels 200 × 200 × 200 μm. The sensitivity of each approach to imaging parameters was explored., Results: The FLASH data showed laminar alignments of voxels with high signal, in keeping with the presumed predominance of contrast in the interstices between sheetlets. It was analysed, using structure-tensor (ST) analysis, to determine the most (v1(ST)), intermediate (v2(ST)) and least (v3(ST)) extended orthogonal directions of signal continuity. The DTI data was analysed to determine the most (e1(DTI)), intermediate (e2(DTI)) and least (e3(DTI)) orthogonal eigenvectors of extent of diffusion. The correspondence between the FLASH and DTI methods was measured and appraised. The most extended direction of FLASH signal (v1(ST)) agreed well with that of diffusion (e1(DTI)) throughout the left ventricle (representative discrepancy in the septum of 13.3 ± 6.7°: median ± absolute deviation) and both were in keeping with the expected local orientations of the long-axis of cardiomyocytes. However, the orientation of the least directions of FLASH signal continuity (v3(ST)) and diffusion (e3(ST)) showed greater discrepancies of up to 27.9 ± 17.4°. Both FLASH (v3(ST)) and DTI (e3(DTI)) where compared to directly measured laminar arrays in the FLASH images. For FLASH the discrepancy between the structure-tensor calculated v3(ST) and the directly measured FLASH laminar array normal was of 9 ± 7° for the lateral wall and 7 ± 9° for the septum (median ± inter quartile range), and for DTI the discrepancy between the calculated v3(DTI) and the directly measured FLASH laminar array normal was 22 ± 14° and 61 ± 53.4°. DTI was relatively insensitive to the number of diffusion directions and to time up to 72 hours post fixation, but was moderately affected by b-value (which was scaled by modifying diffusion gradient pulse strength with fixed gradient pulse separation). Optimal DTI parameters were b = 1000 mm/s(2) and 12 diffusion directions. FLASH acquisitions were relatively insensitive to the image processing parameters explored., Conclusions: We show that ST analysis of FLASH is a useful and accurate tool in the measurement of cardiac microstructure. While both FLASH and the DTI approaches appear promising for mapping of the alignments of myocytes throughout myocardium, marked discrepancies between the cross myocyte anisotropies deduced from each method call for consideration of their respective limitations.

It has been shown by histology that cardiac myocytes are organized into laminae and this structure is important in function, both influencing the spread of electrical activation and enabling myocardial thickening in systole by laminar sliding. We have carried out high-spatial resolution three-dimensional MRI of the ventricular myolaminae of the entire volume of the isolated rat heart after contrast perfusion [dimeglumine gadopentate (Gd-DTPA)]. Four ex vivo rat hearts were perfused with Gd-DTPA and fixative and high-spatial resolution MRI was performed on a 9.4T MRI system. After MRI, cryosectioning followed by histology was performed. Images from MRI and histology were aligned, described, and quantitatively compared. In the three-dimensional MR images we directly show the presence of laminae and demonstrate that these are highly branching and are absent from much of the subepicardium. We visualized these MRI volumes to demonstrate laminar architecture and quantitatively demonstrated that the structural features observed are similar to those imaged in histology. We showed qualitatively and quantitatively that laminar architecture is similar in the four hearts. MRI can be used to image the laminar architecture of ex vivo hearts in three dimensions, and the images produced are qualitatively and quantitatively comparable with histology. We have demonstrated in the rat that: 1) laminar architecture is consistent between hearts; 2) myolaminae are absent from much of the subepicardium; and 3) although localized orthotropy is present throughout the myocardium, tracked myolaminae are branching structures and do not have a discrete identity.

Background: While the microstructure of the left ventricle (LV) has been largely described, only a few studies investigated the right ventricular insertion point (RVIP). It was accepted that the aggregate cardiomyocytes organization was much more complex due to the intersection of the ventricular cavities but a precise structural characterization in the human heart was lacking even if clinical phenotypes related to right ventricular wall stress or arrhythmia were observed in this region. Methods: MRI-derived anatomical imaging (150 µm3) and diffusion tensor imaging (600 µm3) were performed in large mammalian whole hearts (human: N = 5, sheep: N = 5). Fractional anisotropy, aggregate cardiomyocytes orientations and tractography were compared within both species. Aggregate cardiomyocytes orientation on one ex-vivo sheep whole heart was then computed using structure tensor imaging (STI) from 21 µm isotropic acquisition acquired with micro computed tomography (MicroCT) imaging. Macroscopic and histological examination were performed. Lastly, experimental cardiomyocytes orientation distribution was then compared to the usual rule-based model using electrophysiological (EP) modeling. Electrical activity was modeled with the monodomain formulation. Results: The RVIP at the level of the inferior ventricular septum presented a unique arrangement of aggregate cardiomyocytes. An abrupt, mid-myocardial change in cardiomyocytes orientation was observed, delimiting a triangle-shaped region, present in both sheep and human hearts. FA's histogram distribution (mean ± std: 0.29 ± 0.06) of the identified region as well as the main dimension (22.2 mm ± 5.6 mm) was found homogeneous across samples and species. Averaged volume is 0.34 cm3 ± 0.15 cm3. Both local activation time (LAT) and morphology of pseudo-ECGs were strongly impacted with delayed LAT and change in peak-to-peak amplitude in the simulated wedge model. Conclusion: The study was the first to describe the 3D cardiomyocytes architecture of the basal inferoseptal left ventricle region in human hearts and identify the presence of a well-organized aggregate cardiomyocytes arrangement and cardiac structural discontinuities. The results might offer a better appreciation of clinical phenotypes like RVIP-late gadolinium enhancement or uncommon idiopathic ventricular arrhythmias (VA) originating from this region. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular magnetic resonance T1ρ mapping may detect myocardial injuries without exogenous contrast agent. However, multiple co-registered acquisitions are required, and the lack of robust motion correction limits its clinical translation. We introduce a single breath-hold myocardial T1ρ mapping method that includes model-based non-rigid motion correction. Methods: A single-shot electrocardiogram (ECG)-triggered balanced steady state free precession (bSSFP) 2D adiabatic T1ρ mapping sequence that collects five T1ρ-weighted (T1ρw) images with different spin lock times within a single breath-hold is proposed. To address the problem of residual respiratory motion, a unified optimization framework consisting of a joint T1ρ fitting and model-based non-rigid motion correction algorithm, insensitive to contrast change, was implemented inline for fast (~ 30 s) and direct visualization of T1ρ maps. The proposed reconstruction was optimized on an ex vivo human heart placed on a motion-controlled platform. The technique was then tested in 8 healthy subjects and validated in 30 patients with suspected myocardial injury on a 1.5T CMR scanner. The Dice similarity coefficient (DSC) and maximum perpendicular distance (MPD) were used to quantify motion and evaluate motion correction. The quality of T1ρ maps was scored. In patients, T1ρ mapping was compared to cine imaging, T2 mapping and conventional post-contrast 2D late gadolinium enhancement (LGE). T1ρ values were assessed in remote and injured areas, using LGE as reference. Results: Despite breath holds, respiratory motion throughout T1ρw images was much larger in patients than in healthy subjects (5.1 ± 2.7 mm vs. 0.5 ± 0.4 mm, P < 0.01). In patients, the model-based non-rigid motion correction improved the alignment of T1ρw images, with higher DSC (87.7 ± 5.3% vs. 82.2 ± 7.5%, P < 0.01), and lower MPD (3.5 ± 1.9 mm vs. 5.1 ± 2.7 mm, P < 0.01). This resulted in significantly improved quality of the T1ρ maps (3.6 ± 0.6 vs. 2.1 ± 0.9, P < 0.01). Using this approach, T1ρ mapping could be used to identify LGE in patients with 93% sensitivity and 89% specificity. T1ρ values in injured (LGE positive) areas were significantly higher than in the remote myocardium (68.4 ± 7.9 ms vs. 48.8 ± 6.5 ms, P < 0.01). Conclusions: The proposed motion-corrected T1ρ mapping framework enables a quantitative characterization of myocardial injuries with relatively low sensitivity to respiratory motion. This technique may be a robust and contrast-free adjunct to LGE for gaining new insight into myocardial structural disorders. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study is to compare structure tensor imaging (STI) with diffusion tensor imaging (DTI) of the sheep heart (approximately the same size as the human heart). Materials and methods: MRI acquisition on three sheep ex vivo hearts was performed at 9.4 T/30 cm with a seven-element RF coil. 3D FLASH with an isotropic resolution of 150 µm and 3D spin-echo DTI at 600 µm were performed. Tensor analysis, angles extraction and segments divisions were performed on both volumes. Results: A 3D FLASH allows for visualization of the detailed structure of the left and right ventricles. The helix angle determined using DTI and STI exhibited a smooth transmural change from the endocardium to the epicardium. Both the helix and transverse angles were similar between techniques. Sheetlet organization exhibited the same pattern in both acquisitions, but local angle differences were seen and identified in 17 segments representation. Discussion: This study demonstrated the feasibility of high-resolution MRI for studying the myocyte and myolaminar architecture of sheep hearts. We presented the results of STI on three whole sheep ex vivo hearts and demonstrated a good correspondence between DTI and STI. [ABSTRACT FROM AUTHOR]

Objective: The growing adult population with surgically corrected tetralogy of Fallot (TOF) is at risk of arrhythmias and sudden cardiac death. We sought to investigate the contribution of right ventricular (RV) structural and electrophysiological remodelling to arrhythmia generation in a preclinical animal model of repaired TOF (rTOF).Methods and Results: Pigs mimicking rTOF underwent cardiac MRI functional characterisation and presented with pulmonary regurgitation, RV hypertrophy, dilatation and dysfunction compared with Sham-operated animals (Sham). Optical mapping of rTOF RV-perfused wedges revealed a significant prolongation of RV activation time with slower conduction velocities and regions of conduction slowing well beyond the surgical scar. A reduced protein expression and lateralisation of Connexin-43 were identified in rTOF RVs. A remodelling of extracellular matrix-related gene expression and an increase in collagen content that correlated with prolonged RV activation time were also found in these animals. RV action potential duration (APD) was prolonged in the epicardial anterior region at early and late repolarisation level, thus contributing to a greater APD heterogeneity and to altered transmural and anteroposterior APD gradients in rTOF RVs. APD remodelling involved changes in Kv4.3 and MiRP1 expression. Spontaneous arrhythmias were more frequent in rTOF wedges and more complex in the anterior than in the posterior RV.Conclusion: Significant remodelling of RV conduction and repolarisation properties was found in pigs with rTOF. This remodelling generates a proarrhythmic substrate likely to facilitate re-entries and to contribute to sudden cardiac death in patients with rTOF. [ABSTRACT FROM AUTHOR]

Background: Ventricular tachycardia recurrence can occur after ventricular tachycardia ablation because of incomplete and nontransmural ventricular lesion formation. We sought to compare the lesions made by a novel irrigated needle catheter to conventional radiofrequency lesions.Methods and Results: Thirteen female sheep (4.6±0.7 years, 54±8 kg) were studied. In 7 sheep, 60-s radiofrequency applications were performed using an irrigated needle catheter. In 6 sheep, conventional lesions were made using a 4-mm irrigated catheter. 1.5T in vivo and high-density magnetic resonance imaging (9.4T) were performed on explanted hearts from animals receiving needle radiofrequency. Conventional lesion volume was calculated as (1/6)×π×(A×B(2)+C×D(2)/2). Needle lesion volume was measured as Σ(π×r(2))/2 with a slice thickness of 1 mm. The dimensions of all lesions were also measured on gross pathology. Additional histological analysis of the needle lesions was performed. One hundred twenty endocardial left ventricular ablation lesions (conventional, n=60; needle, n=60) were created. At necropsy, more lesions were found using needle versus conventional radiofrequency (90% versus 75%; P<0.05). Comparing needle versus conventional radiofrequency: lesion volume was larger (1030±362 versus 488±384 mm(3); P<0.001), lesion depth was increased (9.9±2.7 versus 5±2.4 mm; P<0.001), and more transmural lesions were created (62.5% versus 17%; P<0.01). Pericardial contrast injection was observed in 4 apical attempts using needle radiofrequency, however, with no adverse effects. Steam pops occurred in 3 attempts using conventional radiofrequency.Conclusions: Irrigated needle ablation is associated with more frequent, larger, deeper, and more often transmural lesions compared with conventional irrigated ablation. This technology might be of value to treat intramural or epicardial ventricular tachycardia substrates resistant to conventional ablation. [ABSTRACT FROM AUTHOR]