Assessment of Myocardial Microstructure in a Murine Model of Obesity-Related Cardiac Dysfunction by Diffusion Tensor Magnetic Resonance Imaging at 7T

David Lohr; Arne Thiele; Max Stahnke; Vera Braun; Elia Smeir; Joachim Spranger; Sebastian Brachs; Robert Klopfleisch; Anna Foryst-Ludwig; Laura M Schreiber; Ulrich Kintscher; Niklas Beyhoff

doi:10.3389/fcvm.2022.839714

Assessment of Myocardial Microstructure in a Murine Model of Obesity-Related Cardiac Dysfunction by Diffusion Tensor Magnetic Resonance Imaging at 7T

Front Cardiovasc Med. 2022 Apr 5:9:839714. doi: 10.3389/fcvm.2022.839714. eCollection 2022.

Authors

David Lohr¹, Arne Thiele^{2

3}, Max Stahnke^{2

3}, Vera Braun^{2

3}, Elia Smeir^{2

3}, Joachim Spranger^{3

4}, Sebastian Brachs^{3

4}, Robert Klopfleisch⁵, Anna Foryst-Ludwig^{2

3}, Laura M Schreiber¹, Ulrich Kintscher^{2

3}, Niklas Beyhoff^{2

3

6

7}

Affiliations

¹ Chair of Molecular and Cellular Imaging, Comprehensive Heart Failure Center (CHFC), University Hospital Wuerzburg, Wuerzburg, Germany.
² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Cardiovascular-Metabolic-Renal Research Center, Berlin, Germany.
³ German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.
⁴ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Endocrinology and Metabolism, Cardiovascular-Metabolic-Renal Research Center, Berlin, Germany.
⁵ Department of Veterinary Pathology, College of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
⁶ Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁷ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Cardiology, Campus Benjamin Franklin, Berlin, Germany.

Abstract

Background: Obesity exerts multiple deleterious effects on the heart that may ultimately lead to cardiac failure. This study sought to characterize myocardial microstructure and function in an experimental model of obesity-related cardiac dysfunction.

Methods: Male C57BL/6N mice were fed either a high-fat diet (HFD; 60 kcal% fat, n = 12) or standard control diet (9 kcal% fat, n = 10) for 15 weeks. At the end of the study period, cardiac function was assessed by ultra-high frequency echocardiography, and hearts were processed for further analyses. The three-dimensional myocardial microstructure was examined ex vivo at a spatial resolution of 100 × 100 × 100 μm³ by diffusion tensor magnetic resonance imaging (DT-MRI) at 7T. Myocardial deformation, diffusion metrics and fiber tract geometry were analyzed with respect to the different myocardial layers (subendocardium/subepicardium) and segments (base/mid-cavity/apex). Results were correlated with blood sample analyses, histopathology, and gene expression data.

Results: HFD feeding induced significantly increased body weight combined with a pronounced accumulation of visceral fat (body weight 42.3 ± 5.7 vs. 31.5 ± 2.2 g, body weight change 73.7 ± 14.8 vs. 31.1 ± 6.6%, both P < 0.001). Obese mice showed signs of diastolic dysfunction, whereas left-ventricular ejection fraction and fractional shortening remained unchanged (E/e' 41.6 ± 16.6 vs. 24.8 ± 6.0, P < 0.01; isovolumic relaxation time 19 ± 4 vs. 14 ± 4 ms, P < 0.05). Additionally, global longitudinal strain was reduced in the HFD group (-15.1 ± 3.0 vs. -20.0 ± 4.6%, P = 0.01), which was mainly driven by an impairment in basal segments. However, histopathology and gene expression analyses revealed no myocardial fibrosis or differences in cardiomyocyte morphology. Mean diffusivity and eigenvalues of the diffusion tensor were lower in the basal subepicardium of obese mice as assessed by DT-MRI (P < 0.05). The three-dimensional fiber tract arrangement of the left ventricle (LV) remained preserved.

Conclusion: Fifteen weeks of high-fat diet induced alterations in myocardial diffusion properties in mice, whereas no remodeling of the three-dimensional myofiber arrangement of the LV was observed. Obese mice showed reduced longitudinal strain and lower mean diffusivity predominantly in the left-ventricular base, and further investigation into the significance of this regional pattern is required.

Keywords: cardiac adipose tissue; cardiac dysfunction; diffusion tensor imaging; high-fat diet; magnetic resonance imaging; obesity; obesity-related cardiac dysfunction.