Quantification of Myocyte Disarray in Human Cardiac Tissue

Year: 2021

Authors: Giardini F., Lazzeri E., Vitale G., Ferrantini C., Costantini I., Pavone FS., Poggesi C., Bocchi L., Sacconi L.

Autors Affiliation: Univ Florence, Lab Nonlinear Spect LENS, Sesto Fiorentino, Italy; Univ Florence, Dept Clin & Expt Med, Div Physiol, Florence, Italy; Univ Florence, Natl Inst Opt, Natl Res Council, Florence, Italy; Univ Florence, Dept Biol, Florence, Italy; Univ Florence, Dept Phys, Florence, Italy; Univ Florence, Dept Informat Engn, Florence, Italy; Univ Freiburg, Fac Med, Inst Expt Cardiovasc Med, Freiburg, Germany.

Abstract: Proper three-dimensional (3D)-cardiomyocyte orientation is important for an effective tension production in cardiac muscle. Cardiac diseases can cause severe remodeling processes in the heart, such as cellular misalignment, that can affect both the electrical and mechanical functions of the organ. To date, a proven methodology to map and quantify myocytes disarray in massive samples is missing. In this study, we present an experimental pipeline to reconstruct and analyze the 3D cardiomyocyte architecture in massive samples. We employed tissue clearing, staining, and advanced microscopy techniques to detect sarcomeres in relatively large human myocardial strips with micrometric resolution. Z-bands periodicity was exploited in a frequency analysis approach to extract the 3D myofilament orientation, providing an orientation map used to characterize the tissue organization at different spatial scales. As a proof-of-principle, we applied the proposed method to healthy and pathologically remodeled human cardiac tissue strips. Preliminary results suggest the reliability of the method: strips from a healthy donor are characterized by a well-organized tissue, where the local disarray is log-normally distributed and slightly depends on the spatial scale of analysis; on the contrary, pathological strips show pronounced tissue disorganization, characterized by local disarray significantly dependent on the spatial scale of analysis. A virtual sample generator is developed to link this multi-scale disarray analysis with the underlying cellular architecture. This approach allowed us to quantitatively assess tissue organization in terms of 3D myocyte angular dispersion and may pave the way for developing novel predictive models based on structural data at cellular resolution.

Journal/Review: FRONTIERS IN PHYSIOLOGY

Volume: 12      Pages from: 750364-1  to: 750364-14

More Information: This project has received fundings from the European Union’s Horizon 202 0 research and innovation programme under grant agreement No 952166 (REPAIR), MUR under the FISR program, project FISR2019_00320, and Regione Toscana, Bando Ricerca Salute 2018, PERCARE project.
KeyWords: 3D cardiomyocyte orientation; 3D FFT; cytoarchitecture reconstruction; disarray quantification; tissue modeling
DOI: 10.3389/fphys.2021.750364

Citations: 5
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