Stelios Angeli1, Nicholas Befera2, Jean-Marc Peyrat3, Evan Calabrese4, George Allan Johnson5, Christakis Constantinides6,7. 1. Department of Mechanical and Manufacturing Engineering, Laboratory of Physiology and Biomedical Imaging, School of Engineering, University of Cyprus, 75 Kalipoleos Avenue, Green Park Building, Nicosia, Cyprus. ste.aggeli@gmail.com. 2. Center for In Vivo Microscopy, Duke University Medical Center, Durham, NC, USA. nicholas.befera@duke.edu. 3. Qatar Robotic Surgery Centre, Qatar Science & Technology Park, Doha, Qatar. jmpeyrat@gmail.com. 4. Center for In Vivo Microscopy, Duke University Medical Center, Durham, NC, USA. evan.calabrese@duke.edu. 5. Center for In Vivo Microscopy, Duke University Medical Center, Durham, NC, USA. gjohnson@duke.edu. 6. Department of Mechanical and Manufacturing Engineering, Laboratory of Physiology and Biomedical Imaging, School of Engineering, University of Cyprus, 75 Kalipoleos Avenue, Green Park Building, Nicosia, Cyprus. Christakis.Constantinides@gmail.com. 7. Chi-Biomedical Limited, 36 Parthenonos Street, Apartment 303, Strovolos, 2021, Nicosia, Cyprus. Christakis.Constantinides@gmail.com.
Abstract
BACKGROUND: The complex cardiac fiber structural organization and spatial arrangement of cardiomyocytes in laminar sheetlets contributes greatly to cardiac functional and contractile ejection patterns. This study presents the first comprehensive, ultra-high resolution, fully quantitative statistical tensor map of the fixed murine heart at isotropic resolution of 43 μm using diffusion tensor (DT) cardiovascular magnetic resonance (CMR). METHODS: Imaging was completed in approximately 12 hours using a six-directional encoding scheme, in five ex vivo healthy C57BL/6 mouse hearts. The tensor map constructed from this data provides an average description of the murine fiber architecture visualized with fiber tractography, and its population variability, using the latest advances in image tensor analysis and statistics. RESULTS: Results show that non-normalized cardiac tensor maps are associated with mean fractional anisotropy of 0.25 ± 0.07 and mean diffusivity of 8.9 ± 1.6 × 10⁻⁴mm²/s. Moreover, average mid-ventricular helical angle distributions ranged between -41 ± 3° and +52 ± 5° and were highly correlated with transmural depth, in agreement with prior published results in humans and canines. Calculated variabilities of local myocyte orientations were 2.0° and 1.4°. Laminar sheet orientation variability was found to be less stable at 2.6°. Despite such variations, the murine heart seems to be highly structured, particularly when compared to canines and humans. CONCLUSIONS: This tensor map has the potential to yield an accurate mean representation and identification of common or unique features of the cardiac myocyte architecture, to establish a baseline standard reference of DTI indices, and to improve detection of biomarkers, especially in pathological states or post-transgenetic modifications.
BACKGROUND: The complex cardiac fiber structural organization and spatial arrangement of cardiomyocytes in laminar sheetlets contributes greatly to cardiac functional and contractile ejection patterns. This study presents the first comprehensive, ultra-high resolution, fully quantitative statistical tensor map of the fixed murine heart at isotropic resolution of 43 μm using diffusion tensor (DT) cardiovascular magnetic resonance (CMR). METHODS: Imaging was completed in approximately 12 hours using a six-directional encoding scheme, in five ex vivo healthy C57BL/6 mouse hearts. The tensor map constructed from this data provides an average description of the murine fiber architecture visualized with fiber tractography, and its population variability, using the latest advances in image tensor analysis and statistics. RESULTS: Results show that non-normalized cardiac tensor maps are associated with mean fractional anisotropy of 0.25 ± 0.07 and mean diffusivity of 8.9 ± 1.6 × 10⁻⁴mm²/s. Moreover, average mid-ventricular helical angle distributions ranged between -41 ± 3° and +52 ± 5° and were highly correlated with transmural depth, in agreement with prior published results in humans and canines. Calculated variabilities of local myocyte orientations were 2.0° and 1.4°. Laminar sheet orientation variability was found to be less stable at 2.6°. Despite such variations, the murine heart seems to be highly structured, particularly when compared to canines and humans. CONCLUSIONS: This tensor map has the potential to yield an accurate mean representation and identification of common or unique features of the cardiac myocyte architecture, to establish a baseline standard reference of DTI indices, and to improve detection of biomarkers, especially in pathological states or post-transgenetic modifications.
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