Novel application of 3D contrast-enhanced CMR to define fibrotic structure of the human sinoatrial node in vivo

Aims The adult human sinoatrial node (SAN) has a specialized fibrotic intramural structure (35-55% fibrotic tissue) that provides mechanical and electrical protection from the surrounding atria. We hypothesize that late gadoliniumenhanced cardiovascular magnetic resonance (LGE-CMR) can be applied to define the fibrotic human SAN structure in vivo. Methods and results LGE-CMR atrial scans of healthy volunteers (n olu, 23-52 y.o.) using a 3 Tesla magnetic resonance imaging system with a spatial resolution of 1.0 mm³ or 0.625 × 0.625 × 1.25 mm³ were obtained and analysed. Percent fibrosis of total connective and cardiomyocyte tissue area in segmented atrial regions were measured based on signal intensity differences of fibrotic vs. non-fibrotic cardiomyocyte tissue. A distinct ellipsoidal fibrotic region (length: 23.6 ± 1.9 mm; width: 7.2 ± 0.9 mm; depth: 2.9 ± 0.4 mm) in all hearts was observed along the posterior junction of the crista terminalis and superior vena cava extending towards the interatrial septum, corresponding to the anatomical location of the human SAN. The SAN fibrotic region consisted of 41.9 ± 5.4% of LGE voxels above an average threshold of 2.7 SD (range 2-3 SD) from the non-fibrotic right atrial free wall tissue. Fibrosis quantification and SAN identification by in vivo LGE-CMR were validated in optically mapped explanted donor hearts ex vivo (n ivo, 19-65 y.o.) by contrast-enhanced CMR (9.4 Tesla; up to 90 mm3 resolution) correlated with serial histological sections of the SAN. Conclusion This is the first study to visualize the 3D human SAN fibrotic structure in vivo using LGE-CMR. Identification of the 3D SAN location and its high fibrotic content by LGE-CMR may provide a new tool to avoid or target SAN structure during ablation.