Maximilian Müller ^1,2,3 Elias Daud ^1,2,3,4 Georg Langer ¹ Jan Gröschel ^1,2,3,5 Darian Viezzer ^1,2,3 Thomas Hadler ^1,2,3 Ning Jin ⁶ Daniel Giese ^7,8 Sebastian Schmitter ^10,11,9 Jeanette Schulz-Menger ^1,12,2,3* Ralf Felix Trauzeddel ^1,13,2,3

• ¹ Charité University Medicine Berlin, Berlin, Germany
• ² Experimental and Clinical Research Center, Charite University Medicine Berlin, Berlin, Baden-Wurttemberg, Germany
• ³ Partner site Berlin, German Center for Cardiovascular Research (DZHK), Berlin, Berlin, Germany
• ⁴ Faculty of Medicine, Bar-Ilan University, Safed, Tel Aviv, Israel
• ⁵ German Heart Center Berlin, Berlin, Baden-Wurttemberg, Germany
• ⁶ Cardiovascular MR R&D, Siemens Medical Solutions USA, Inc., Cleveland, Ohio, United States
• ⁷ Cardiovascular MR R&D, Siemens Healthcare GmbH, Erlangen, Germany
• ⁸ Institute of Radiology, University Hospital Erlangen, Erlangen, Bavaria, Germany
• ⁹ Physical-Technical Federal Institute, Braunschweig/Brunswick, Niedersachsen, Germany
• ¹⁰ Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota, United States
• ¹¹ Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany
• ¹² Department of Cardiology and Nephrology, HELIOS Klinikum Berlin Buch, 13125, Berlin, Germany
• ¹³ Charité - Universitätsmedizin Berlin, Department of Anesthesiology and Intensive Care Medicine, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany

Background: Time-resolved 3D cine phase-contrast cardiovascular magnetic resonance (4D Flow CMR) enables the characterization of blood flow using basic and advanced hemodynamic parameters. However, different confounders, e.g. different field strength, scanner configurations or sequences, might impact 4D Flow CMR measurements. The aim of this study was to analyze inter-site reproducibility of 4D Flow CMR to determine the influence of said confounders. Methods: A cohort of 19 healthy travelling volunteers underwent 4D Flow CMR at four different sites (Site I-III: 3T scanner, Site IV: 1.5T scanner; all Siemens Healthineers, Erlangen, Germany). Two protocols of one 4D Flow CMR research sequence were performed, one acquiring velocity vectors fields in the thoracic aorta only and one in the entire heart and thoracic aorta combined. Basic and advanced hemodynamic parameters, i.e. forward flow volume (FFV), peak and mean velocities (Vp and Vm), and wall shear stress (3D WSS) at nine different planes across the thoracic aorta (P1-2 ascending aorta, P3-5 aortic arch, P6-9 descending aorta) were analyzed. Based on a second scan at site I mean values and tolerance ranges (TOL) were generated for inter-site comparison. Equivalency was assumed, when confidence intervals of sites II-IV laid within such TOL. Additionally, inter- and intra-observer analysis as well as a comparison between the two protocols was performed, using intraclass correlation coefficient (ICC). Results: Inter-site comparability showed equivalency in P1 and P2 for FFV, Vp and Vm at all sites. Non-equivalency was present in various planes of P3-9 and in P2 for 3D WSS in one protocol. In total, site IV showed the most disagreements. Protocol comparison yielded excellent (>0.9) ICC in every plane for FFV, good (0.75-0.9) to excellent ICC for Vm and 3D WSS, good to excellent ICC in eight planes for Vp and moderate (0.5-0.75) ICC in one plane for Vp. Inter- and intra-observer analysis showed excellent agreement for every parameter. Conclusions: Basic and advanced hemodynamic parameters revealed equivalency at different sites and field strength in the ascending aorta, a clinically important region of interest, under a highly controlled environment.