Myofiber Architecture of the Human Atria as Revealed by Submillimeter Diffusion Tensor Imaging

Abstract

Background: Accurate knowledge of the human atrial fibrous structure is paramount in understanding the mechanisms of atrial electric function in health and disease. Thus far, such knowledge has been acquired from destructive sectioning, and there is a paucity of data about atrial fiber architecture variability in the human population.

Methods and results: In this study, we have developed a customized 3-dimensional diffusion tensor magnetic resonance imaging sequence on a clinical scanner that makes it possible to image an entire intact human heart specimen ex vivo at submillimeter resolution. The data from 8 human atrial specimens obtained with this technique present complete maps of the fibrous organization of the human atria. The findings demonstrate that the main features of atrial anatomy are mostly preserved across subjects although the exact location and orientation of atrial bundles vary. Using the full tractography data, we were able to cluster, visualize, and characterize the distinct major bundles in the human atria. Furthermore, quantitative characterization of the fiber angles across the atrial wall revealed that the transmural fiber angle distribution is heterogeneous throughout different regions of the atria.

Conclusions: The application of submillimeter diffusion tensor magnetic resonance imaging provides an unprecedented level of information on both human atrial structure, as well as its intersubject variability. The high resolution and fidelity of this data could enhance our understanding of structural contributions to atrial rhythm and pump disorders and lead to improvements in their targeted treatment.

Keywords: arrhythmias, cardiac; atrial function; atrial myoarchitecture; diffusion magnetic resonance imaging; diffusion tensor imaging; fiber orientation; heart atria.

Figure 1:

Acquired geometry and fiber visualization results in human atria specimens. (Left panel) Atrial geometry: (A) Short-axis view of a non-diffusion weighted image (b0) with superimposed segmentation of left atrium (LA, red), right atrium (RA, blue) and inter-atrial bundles (green). Fat tissue surrounding the atria is excluded from the segmentation. (B) Anterior view of left and right atria created from T1-weighted images; the dark grey volume represents lumen. (Right panel): Fiber visualization using tractography. (C) Posterior view of atrial roof. (D) Anterior view. (E) Inferior and left lateral view. (F) View of right atrium. Color encodes the local distance to the endocardial shell: yellow is the endocardial layer, and red is the epicardial layer. (LIPV: Left inferior pulmonary vein, LSPV: Left superior pulmonary vein, RIPV: Right inferior pulmonary vein, RSPV: Right superior pulmonary vein, LAA: Left atrial appendage, RAA: Right atrial appendage, IVC: inferior vena cava, SVC: superior vena cava, MV: Mitral valve, TV: Tricuspid valve, BB: Bachman bundle)

Figure 2:

Fiber tractography in eight hearts as viewed posteriorly over the roof of the LA. The lumen of each atrium is colored gray. Color-coding is as in Figure 1C–F. The schematic at the bottom right shows the “horizontal” direction defined by the four origins of the PVs, as described in Methods. Fiber angles on the roof of the posterior wall are measured with respect to that horizontal (marked LR in schematic). Average fiber angles at the roof were calculated in the region outlined by the dashed box.

Figure 3:

Fiber tractography of human atria (specimen 1) at different transmural layers as viewed from the Posterior (A) and Anterior (B) sides. The right column presents the original tracts. Left and middle columns represent the same results with sub-endocardial and sub-epicardial cuts, such that the outer layer fibers (at higher distances from the endocardium) have been removed from the visualization. The tracts have been visualized at a higher density (less culling down – see Supplementary Methods) in comparison to Figs 1 and 2. The color-encoding is based on the distance from the endocardial shell.

Figure 4:

Regional changes in fiber orientation across the atrial wall. (A) (top) posterior view of the LA of specimen 4; (middle), a histogram of the transmural distribution of fiber angles from two ROIs; and (bottom), the transmural profile of fiber angles as a function of atrial wall depth in ROIs A and B. (B) Posterior lateral view of the maps of transmural angle dispersion for the eight specimens. (C) Same as (A) in sample 1. (D) Anterior view of the maps of transmural angle dispersion.

Figure 5:

The major fiber bundles in the human LA. (A-C) Posterior; (D,E) Anterior view, and (F) Septum. The individual bundles are denoted a-l in heart 7.

Figure 6:

Endocardial view of the right atrium of specimen 4. (A) 3D rendering of trabeculated structure reconstructed from non-diffusion weighted MR images and (B) the corresponding fiber tracts overlaid on top. The pectinate muscles and crista terminalis of the right atrium are manifested as dense tracts in tractography results. The orientation of these fiber tracts follows the trabeculated structure of the endocardial wall (A).