Patricia Garcia-Canadilla1,2, Hector Dejea3,4, Anne Bonnin3, Vedrana Balicevic5, Sven Loncaric5, Chong Zhang2, Constantine Butakoff2, Jazmin Aguado-Sierra6, Mariano Vázquez6,7, Laurence H Jackson8, Daniel J Stuckey8, Cristoph Rau9, Marco Stampanoni3,4, Bart Bijnens2,10, Andrew C Cook1. 1. Institute of Cardiovascular Science (P.G.-C., A.C.C.), University College London, United Kingdom. 2. Department of Information and Communications Technologies, Universitat Pompeu Fabra, Barcelona, Spain (P.G.-C., C.Z., C.B., B.B.). 3. Swiss Light Source, Paul Scherrer Institut, Villigen, Switzerland (H.D., A.B., M.S.). 4. Institute for Biomedical Engineering, ETH Zurich, Zurich, Switzerland (H.D., M.S.). 5. Faculty of Electrical Engineering and Computing, University of Zagreb, Zagreb, Croatia (V.B., S.L.). 6. Barcelona Supercomputing Center-Centro Nacional de Supercomputación, Campus Nord Universitat Politecnica de Catalunya, Barcelona, Spain (J.A.-S., M.V.). 7. IIIA-CSIC, Bellaterra, Spain (M.V.). 8. Division of Medicine, Centre for Advanced Biomedical Imaging (L.H.J., D.J.S.), University College London, United Kingdom. 9. Diamond Manchester Imaging Branchline (I13-2), Diamond Lightsource, Oxford, United Kingdom (C.R.). 10. Institución Catalana de Investigación y Estudios Avanzados, Barcelona, Spain (B.B.).
Abstract
BACKGROUND: In the era of increasingly successful corrective interventions in patients with congenital heart disease (CHD), global and regional myocardial remodeling are emerging as important sources of long-term morbidity/mortality. Changes in organization of the myocardium in CHD, and in its mechanical properties, conduction, and blood supply, result in altered myocardial function both before and after surgery. To gain a better understanding and develop appropriate and individualized treatment strategies, the microscopic organization of cardiomyocytes, and their integration at a macroscopic level, needs to be completely understood. The aim of this study is to describe, for the first time, in 3 dimensions and nondestructively the detailed remodeling of cardiac microstructure present in a human fetal heart with complex CHD. METHODS AND RESULTS: Synchrotron X-ray phase-contrast imaging was used to image an archival midgestation formalin-fixed fetal heart with right isomerism and complex CHD and compare with a control fetal heart. Analysis of myocyte aggregates, at detail not accessible with other techniques, was performed. Macroanatomic and conduction system changes specific to the disease were clearly observable, together with disordered myocyte organization in the morphologically right ventricle myocardium. Electrical activation simulations suggested altered synchronicity of the morphologically right ventricle. CONCLUSIONS: We have shown the potential of X-ray phase-contrast imaging for studying cardiac microstructure in the developing human fetal heart at high resolution providing novel insight while preserving valuable archival material for future study. This is the first study to show myocardial alterations occur in complex CHD as early as midgestation.
BACKGROUND: In the era of increasingly successful corrective interventions in patients with congenital heart disease (CHD), global and regional myocardial remodeling are emerging as important sources of long-term morbidity/mortality. Changes in organization of the myocardium in CHD, and in its mechanical properties, conduction, and blood supply, result in altered myocardial function both before and after surgery. To gain a better understanding and develop appropriate and individualized treatment strategies, the microscopic organization of cardiomyocytes, and their integration at a macroscopic level, needs to be completely understood. The aim of this study is to describe, for the first time, in 3 dimensions and nondestructively the detailed remodeling of cardiac microstructure present in a human fetal heart with complex CHD. METHODS AND RESULTS: Synchrotron X-ray phase-contrast imaging was used to image an archival midgestation formalin-fixed fetal heart with right isomerism and complex CHD and compare with a control fetal heart. Analysis of myocyte aggregates, at detail not accessible with other techniques, was performed. Macroanatomic and conduction system changes specific to the disease were clearly observable, together with disordered myocyte organization in the morphologically right ventricle myocardium. Electrical activation simulations suggested altered synchronicity of the morphologically right ventricle. CONCLUSIONS: We have shown the potential of X-ray phase-contrast imaging for studying cardiac microstructure in the developing human fetal heart at high resolution providing novel insight while preserving valuable archival material for future study. This is the first study to show myocardial alterations occur in complex CHD as early as midgestation.
Authors: Jose Novo Matos; Patricia Garcia-Canadilla; Ian C Simcock; J Ciaran Hutchinson; Melanie Dobromylskyj; Anna Guy; Owen J Arthurs; Andrew C Cook; Virginia Luis Fuentes Journal: Sci Rep Date: 2020-11-19 Impact factor: 4.379