PDF(Pubmed)
Abstract：
Intramural fibrosis represents a crucial factor in the formation of a three-dimensional (3D) substrate for atrial fibrillation (AF). However, the transmural distribution of fibrosis and its relationship with atrial overload remain largely unknown. The aim of this study is to quantify the transmural profile of atrial fibrosis in patients with different degrees of atrial dilatation and arrhythmic profiles by a high-resolution 3D histology method.
Serial microtome-cut tissue slices, sampling the entire atrial wall thickness at 5 µm spatial resolution, were obtained from right atrial appendage specimens in 23 cardiac surgery patients. Atrial slices were picrosirius red stained, imaged by polarized light microscopy, and analysed by a custom-made segmentation algorithm. In all patients, the intramural fibrosis content displayed a progressive decrease alongside tissue depth, passing from 68.6 ± 11.6% in the subepicardium to 10-13% in the subendocardium. Distinct transmural fibrotic profiles were observed in patients with atrial dilatation with respect to control patients, where the first showed a slower decrease of fibrosis along tissue depth (exponential decay constant: 171.2 ± 54.5 vs. 80.9 ± 24.4 µm, P < 0.005). Similar slow fibrotic profiles were observed in patients with AF (142.8 ± 41.7 µm). Subepicardial and midwall levels of fibrosis correlated with the degree of atrial dilatation (ρ = 0.72, P < 0.001), while no correlation was found in subendocardial layers.
Quantification of fibrosis transmural profile at high resolution is feasible by slice-to-slice histology. Deeper penetration of fibrosis in subepicardial and midwall layers in dilated atria may concur to the formation of a 3D arrhythmic substrate.
Serial microtome-cut tissue slices, sampling the entire atrial wall thickness at 5 µm spatial resolution, were obtained from right atrial appendage specimens in 23 cardiac surgery patients. Atrial slices were picrosirius red stained, imaged by polarized light microscopy, and analysed by a custom-made segmentation algorithm. In all patients, the intramural fibrosis content displayed a progressive decrease alongside tissue depth, passing from 68.6 ± 11.6% in the subepicardium to 10-13% in the subendocardium. Distinct transmural fibrotic profiles were observed in patients with atrial dilatation with respect to control patients, where the first showed a slower decrease of fibrosis along tissue depth (exponential decay constant: 171.2 ± 54.5 vs. 80.9 ± 24.4 µm, P < 0.005). Similar slow fibrotic profiles were observed in patients with AF (142.8 ± 41.7 µm). Subepicardial and midwall levels of fibrosis correlated with the degree of atrial dilatation (ρ = 0.72, P < 0.001), while no correlation was found in subendocardial layers.
Quantification of fibrosis transmural profile at high resolution is feasible by slice-to-slice histology. Deeper penetration of fibrosis in subepicardial and midwall layers in dilated atria may concur to the formation of a 3D arrhythmic substrate.
摘要：
目的：壁内纤维化是心房颤动（AF）三维（3D）基质形成的关键因素。然而,纤维化的透壁分布及其与心房超负荷的关系仍然未知。本研究的目的是通过高分辨率3D组织学方法量化具有不同程度心房扩张和心律失常特征的患者心房纤维化的透壁特征。
结果：连续切片机切片，以5µm的空间分辨率对整个心房壁厚度进行采样，从23例心脏手术患者的右心耳标本中获得。心房切片被picrosirius红染色，通过偏振光显微镜成像，并通过定制的分割算法进行分析。在所有患者中，壁内纤维化含量随着组织深度逐渐减少，从心下膜的68.6±11.6％过渡到心内膜下的10-13％。与对照组患者相比，在心房扩张患者中观察到明显的透壁纤维化特征。其中第一个显示沿组织深度的纤维化降低较慢（指数衰减常数：171.2±54.5与80.9±24.4µm，P<0.005)。在房颤患者中观察到类似的缓慢纤维化特征(142.8±41.7µm)。心外膜和中壁纤维化水平与心房扩张程度相关(ρ=0.72,P<0.001),而在心内膜下层没有发现相关性。
结论：通过切片组织学对纤维化透壁图进行高分辨率定量是可行的。扩张心房的心外膜下和中壁层中纤维化的更深渗透可能与3D心律失常基质的形成相一致。
结果：连续切片机切片，
结论：通过切片组织学对纤维化透壁图进行高分辨率定量是可行的。
