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We present accurate 3D representations of the location of the cardiac conduction system in the intact human heart using the non-destructive imaging technique of contrast enhanced micro-CT. Contrast enhancement permits us to distinguish the relevant tissue types based on their differential attenuation of the x-ray beam. As a result of iodine infusion; fat, working myocardium, specialised nodal tissue, paranodal tissue, and connective tissue exhibit decreasing levels of attenuation respectively, and thus decreasing voxel values in the tomographic data. We have discussed previously the possible mechanism behind the observed differential uptake of iodine by biological tissues12, 38. The spatial resolution obtained was also sufficient to demonstrate cardiomyocyte orientation, thus permitting us to produce an anatomically and biophysically detailed mathematical model of cardiac electrical activation.
We have revealed multiple myocyte projections that emerge from the sinus node to enter the atrial working myocardium (Fig. 2 and Supplementary Figs S1 and S2). These projections had similar voxel values to the paranodal areas, and could be potential exit pathways from the sinus node. The presence of such pathways has been debated for many years33, 34, 44. Optical mapping in the region suggests that there are distinct sites of breakthrough for activation of the atrial myocardium34, 35, 45. In a histological study by Sanchez-Quintana et al. (2005) extensions were found to project from the head, body and tail regions of the sinus node. Consistent with those findings, we resolved projections running towards the endocardial region of the terminal crest, and also towards the epicardial surface. Our high-resolution data suggest that direct connections towards the pectinate muscles may also exist (Fig. 2 and Supplementary Fig. S1). The paranodal area has the potential to act as a pacemaker, and many tachycardias in man have been observed to originate from the region of the terminal crest14, 22. In this regard, our data has potential use in computer modelling studies investigating the function of the paranodal area, and the role of these apparent exit pathways, previously shown only in 2D histological sections44, 45. 59ce067264
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