Anatomically correct assessment of the orientation of the cardiomyocytes using diffusion tensor imaging

Abstract

Diffusion tensor imaging has been used for assessing the orientation of cardiac myocytes for decades. Striking methodological differences exist between studies when quantifying these orientations. This limits the comparability between studies, and impedes collaboration and the drawing of appropriate physiological conclusions.We have sought to elucidate these differences, permitting us to propose a standardised "tool set" that might better establish consensus in future studies.We fixed hearts from seven 25 kg pigs in formalin, and scanned them using diffusion tensor imaging. Using various angle definitions as found in literature, we assessed the orientations of cardiomyocytes, comparing them in terms of helical and intrusion angles, along with the orientation of their aggregations. The difference between assessment of the helical angle with and without relation to the epicardial curvature was 25.2°(SD: 7.9) at the base, 5.8°(1.9) at the equatorial level, and 28.0°(7.0) at the apex, ANOVA P = 0.001. In comparable fashion, the intrusion angle differed by 25.9°( 12.9), 7.6°(0.98) and 17.5°(4.7), P = 0.01, and the angle of the aggregates (E3-angle) differed by 25.0°(13.5) at the base, 9.4°(1.7) at the equator, and 23.1°(6.2) apically, P = 0.003. When assessing 14 definitions used in literature to calculate the orientation of aggregates, only 4 rendered identical results. The findings show that any attempt to use projection of eigenvectors introduces considerable bias. The epicardial curvature of the ventricular cone needs to be taken into account when seeking to provide accurate quantification of the orientation of the aggregated cardiomyocytes, especially in the apical and basal regions. This means that projection of eigenvectors should be avoided prior to quantifying myocyte orientation, especially when assessing radial orientation. Based on our results, we suggest appropriate methods for valid assessment of myocyte orientation using diffusion tensor imaging.

Measurement of local orientation of cardiomyocyte aggregates in human left ventricle free wall samples using X-ray phase-contrast microtomography

“…The local orientation of myocyte aggregates can be described by different pairs of angles, not exactly the same. Such angles are the helix angle (HA) and the transverse angle (TA) [13,53], the elevation angle and the azimuth angle [22,21,30], and the helical angle and the intrusion angle [47,8,1]. We chose the HA and TA for this study, because they are still the most used angles in the literature, and knowing that the method we develop here can be used with whichever angle definition is preferred.…”

Diffusion tensor imaging and arterial tissue: establishing the influence of arterial tissue microstructure on fractional anisotropy, mean diffusivity and tractography

“…Fibre tractography has also been shown to be sensitive to the time-dependent orientation of collagen fibres in biodegradable tissue engineered constructs seeded with human-derived vascular cells 20 . Similarly, the orientation of cardiomyocytes 21,22 has been illustrated by tractography, as well as the differentiation between healthy and diseased cardiac architecture [23][24][25] . Together, these studies allude to the ability of DTI metrics to be selectively sensitive to specific microstructural components, but this has yet to be conclusively determined in arterial tissue.…”

An Appreciation of Anatomy in the Molecular World

“…Analyses of the spiraling organization is becoming quite sophisticated with the introduction of MRI and CT-based measurements enabling diffusion tensor imaging and tractography, respectively [ 53 , 61 ]. Nonetheless, one can reasonably posit that it is not obvious what the functional significance is of steeper or flatter helical angles, although experiments and case–control studies do show that hypertrophy of the ventricular walls associates with helical angles that deviate from normal [ 62 , 63 ].…”

“…The trabecular muscle of the left ventricle comprises only some 15% of the normal ventricular mass, the rest being compact wall [ 69 ]. While detailed analysis of the structure of the compact wall as geodesic lines can be made [ 61 ], the complex organization of the trabecular mass is more difficult to analyze [ 44 ]. Trabeculae are thought to increase wall stiffness [ 70 ] and negatively impact on the maximal stroke volume [ 71 ], in addition to facilitating thrombus formation like the trabecular muscle of the left atrial appendage [ 72 ] in atrial fibrillation [ 73 ].…”