Wheel running in mice promotes physiological remodeling in the heart in coordination with spatial upregulations of CITED4 a Representative DT-MRI images of helicity changes from the endocardium to epicardium between sedentary and exercised mice in cohort 1. b–d Helicity differences within the septum, lateral wall and averaged across all AHA sections. e Magnified representative images of DAPI and CITED4 within the septal and lateral wall regions within exercised and sedentary mice. f–h CITED4 signal in sedentary and exercised mice within the septum, lateral wall and averaged across all AHA sections. Unpaired two-tailed t-test. *P < 0.05, **P < 0.01, ***P < 0.001. Data are presented min to max. Within each box, horizontal black and red lines denote median values; boxes extend from the 25th to the 75th percentile of each group’s distribution of values.
Both exercise-induced molecular mechanisms and physiological cardiac remodeling have been previously studied on a whole heart level. However, the regional microstructural tissue effects of these molecular mechanisms in the heart have yet to be spatially linked and further elucidated. We show in exercised mice that the expression of CITED4, a transc...
Description of the cardiac myofiber architecture in pathological or even physiological conditions is essential for image-based modeling in electrophysiology or mechanical studies. While diffusion tensor imaging (DTI) is one of the best modalities to capture myofiber orientation of large mammalian hearts, validations of putative myofiber’s main orientation from DTI in whole hearts of large mammals is limited. First we design an experimental protocol for sheep (N = 1) and human (N = 1) whole hearts that combine a standardized sample preparation with high-resolution diffusion MRI at 600 µm3 using low angular resolution (6 directions) followed by a tissue air-drying approach coupled with X-ray imaging at 42 µm3. Secondly, we propose a standardized post-processing pipeline for symmetric multimodal mapping allowing the comparison of myofiber orientation computed from DTI and structure tensor imaging (STI), respectively. We then identified region-of-interest (ROI) exhibiting small or sharp spatial variations in myofiber orientation and compared the putative myofiber orientation for both methods. In conclusion, we show a good correspondence of structural features between the two imaging modalities and identify new unexpected and complex cardiomyocytes organization such as oscillating patterns or clear separation of opposing fiber-bundles.KeywordsCardiac myofiber architectureDiffusion MRIMicroCTLarge mammalian whole heartsRegistration