title: Novel application of 3D contrast-enhanced CMR to define fibrotic structure of the human sinoatrial node in vivo.
abstract: OBJECTIVE
  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 gadolinium-enhanced cardiovascular magnetic resonance (LGE-CMR) can be applied to define the fibrotic human SAN structure in vivo.
  
  
  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 µm3 resolution) correlated with serial histological sections of the SAN.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Csepe
authors.affiliation: Auckland Bioengineering Institute, The University of Auckland, 70 Symonds Street, Auckland 1142, 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, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA.
authors.forename: Lidiya V
authors.initials: LV
authors.lastname: Sul
authors.affiliation: Auckland Bioengineering Institute, The University of Auckland, 70 Symonds Street, Auckland 1142, New Zealand.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, 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, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Ignozzi
authors.affiliation: Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA.|Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, 473 W 12th Avenue, Columbus, OH 43210, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Bratasz
authors.affiliation: Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA.|Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, 473 W 12th Avenue, Columbus, OH 43210, USA.
authors.forename: Kimerly A
authors.initials: KA
authors.lastname: Powell
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, 473 W 12th Avenue, Columbus, OH 43210, USA.|Department of Surgery, The Ohio State University Wexner Medical Center, 410 W 10th Avenue, Columbus, OH 43210, USA.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Kilic
authors.affiliation: Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA.|Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, 473 W 12th Avenue, Columbus, OH 43210, USA.|Department of Internal Medicine, The Ohio State University Wexner Medical Center, 395 W 12th Avenue, Columbus, OH 43210, 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, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA.|Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, 473 W 12th Avenue, Columbus, OH 43210, USA.|Department of Internal Medicine, The Ohio State University Wexner Medical Center, 395 W 12th Avenue, Columbus, OH 43210, USA.
authors.forename: Paul M L
authors.initials: PML
authors.lastname: Janssen
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, 473 W 12th Avenue, Columbus, OH 43210, USA.|Department of Internal Medicine, The Ohio State University Wexner Medical Center, 395 W 12th Avenue, Columbus, OH 43210, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Hummel
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, 473 W 12th Avenue, Columbus, OH 43210, USA.|Department of Biomedical Informatics, The Ohio State University Wexner Medical Center, 250 Lincoln Tower, 1800 Cannon Drive, Columbus, OH 43210, USA.
authors.forename: Orlando P
authors.initials: OP
authors.lastname: Simonetti
authors.affiliation: Department of Physiology & Cell Biology, The Ohio State University Wexner Medical Center, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA.|Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, 473 W 12th Avenue, Columbus, OH 43210, USA.
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Fedorov
mesh_terms: D000328:Adult; D003287:Contrast Media; D005260:Female; D005355:Fibrosis / Q000000981:diagnostic imaging / Q000473:pathology; D005682:Gadolinium; D064368:Healthy Volunteers; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011856:Radiographic Image Enhancement; D012680:Sensitivity and Specificity; D012849:Sinoatrial Node / Q000000981:diagnostic imaging* / Q000473:pathology; D055815:Young Adult
chemical_list: D003287:Contrast Media; D005682:Gadolinium
keywords: fibrosis ; human atria; late gadolinium-enhanced CMR ; optical mapping ; sinoatrial node 