title: Human sinoatrial node structure: 3D microanatomy of sinoatrial conduction pathways.
abstract: BACKGROUND
  Despite a century of extensive study on the human sinoatrial node (SAN), the structure-to-function features of specialized SAN conduction pathways (SACP) are still unknown and debated. We report a new method for direct analysis of the SAN microstructure in optically-mapped human hearts with and without clinical history of SAN dysfunction.
  
  
  METHODS
  Two explanted donor human hearts were coronary-perfused and optically-mapped. Structural analyses of histological sections parallel to epicardium (∼13-21 μm intervals) were integrated with optical maps to create 3D computational reconstructions of the SAN complex. High-resolution fiber fields were obtained using 3D Eigen-analysis of the structure tensor, and used to analyze SACP microstructure with a fiber-tracking approach.
  
  
  RESULTS
  Optical mapping revealed normal SAN activation of the atria through a lateral SACP proximal to the crista terminalis in Heart #1 but persistent SAN exit block in diseased Heart #2. 3D structural analysis displayed a functionally-observed SAN border composed of fibrosis, fat, and/or discontinuous fibers between SAN and atria, which was only crossed by several branching myofiber tracts in SACP regions. Computational 3D fiber-tracking revealed that myofiber tracts of SACPs created continuous connections between SAN #1 and atria, but in SAN #2, SACP region myofiber tracts were discontinuous due to fibrosis and fat.
  
  
  CONCLUSIONS
  We developed a new integrative functional, structural and computational approach that allowed for the resolution of the specialized 3D microstructure of human SACPs for the first time. Application of this integrated approach will shed new light on the role of the specialized SAN microanatomy in maintaining sinus rhythm.
authors.affiliation: Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Csepe
authors.affiliation: Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.
authors.forename: Jichao
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Hansen
authors.affiliation: Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Lidiya V
authors.initials: LV
authors.lastname: Sul
authors.affiliation: Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.
authors.forename: Praise
authors.initials: P
authors.lastname: Lim
authors.affiliation: Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, USA; Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Orlando P
authors.initials: OP
authors.lastname: Simonetti
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Kilic
authors.affiliation: Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mohler
authors.affiliation: Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Paul M L
authors.initials: PM
authors.lastname: Janssen
authors.affiliation: Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address: fedorov.2@osu.edu.
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Fedorov
mesh_terms: D001683:Biological Clocks; D006329:Heart Conduction System / Q000033:anatomy & histology* / Q000166:cytology / Q000502:physiology; D006801:Humans; D008953:Models, Anatomic; D012849:Sinoatrial Node / Q000033:anatomy & histology* / Q000166:cytology / Q000502:physiology*
keywords: 3D reconstruction; Fibrosis; Human sinoatrial node; Optical mapping; Sinoatrial conduction pathway; Sinus node dysfunction