Regional variations in ex-vivo diffusion tensor anisotropy are associated with cardiomyocyte remodeling in rats after left ventricular pressure overload

Abstract

Background: Pressure overload left ventricular (LV) hypertrophy is characterized by increased cardiomyocyte width and ventricle wall thickness, however the regional variation of this remodeling is unclear. Cardiovascular magnetic resonance (CMR) diffusion tensor imaging (DTI) may provide a non-invasive, comprehensive, and geometrically accurate method to detect regional differences in structural remodeling in hypertrophy. We hypothesized that DTI parameters, such as fractional and planar anisotropy, would reflect myocyte remodeling due to pressure overload in a regionally-dependent manner. Methods: We investigated the regional distributions of myocyte remodeling in rats with or without transverse aortic constriction (TAC) via direct measurement of myocyte dimensions with confocal imaging of thick tissue sections, and correlated myocyte cross-sectional area and other geometric features with parameters of diffusivity from ex-vivo DTI in the same regions of the same hearts. Results: We observed regional differences in several parameters from DTI between TAC hearts and SHAM controls. Consistent with previous studies, helix angles from DTI correlated strongly with those measured directly from histological sections (p < 0.001, R 2 = 0.71). There was a transmural gradient in myocyte cross-sectional area in SHAM hearts that was diminished in the TAC group. We also found several regions of significantly altered DTI parameters in TAC LV compared to SHAM, especially in myocyte sheet angle dispersion and planar anisotropy. Among others, these parameters correlated significantly with directly measured myocyte aspect ratios. Conclusions: These results show that structural remodeling in pressure overload LV hypertrophy is regionally heterogeneous, especially transmurally, with a greater degree of remodeling in the sub-endocardium compared to the sub-epicardium. Additionally, several parameters derived from DTI correlated significantly with measurements of myocyte geometry from direct measurement in histological sections. We suggest that DTI may provide a noninvasive, comprehensive method to detect regional structural myocyte LV remodeling during disease.

Structure-Function in Helical Cardiac Musculature Using Additive Textile Manufacturing

“…Demonstrating this, we have shown how cardiac myofibril alignment regulates ventricular performance, confirming theoretical predictions made over fifty years prior (7). These results suggest that a reduction in helical architecture can alter cardiac performance, reminiscent of some pathological cases such as the increased circumferential strain (38) and reduced ejection fractions observed in hypertensive patients (4,6). This lends support to emerging clinical approaches using conical ventricle reshaping to address heart failure (39,40).…”

“…The heart is organized in a helical fashion, with cardiomyocytes in the left ventricle smoothly transitioning transmurally from a left-to right-handed helix (1). In some cardiomyopathies this organization can be disrupted by maladaptive tissue remodeling (2,3), leading to a more circumferential organization of the myofibrils (3)(4)(5)(6). For more than fifty years, it has been argued that this helical alignment represents a fundamental structure-function relationship which is critical for achieving large ejection fractions (EF) (1,7,8).…”

“…Cardiac myofibrils are organized helically (1), as seen in the cross section of a rodent's heart (Fig S7). Cardiomyopathies such as hypertension (4,6), or mitral valve regurgitation (5), can disrupt this myofibril organization leading to the loss of helical alignments and reorganization into more circumferential geometries (3)(4)(5)(6). While the impact of myocardial fiber alignment on cardiac function has been studied in vivo (10,11,27), these studies are characterized by concomitant changes in protein expression and metabolism (28).…”

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.…”

Cardiac mechanostructure: Using mechanics and anisotropy as inspiration for developing epicardial therapies in treating myocardial infarction

“…Disruption of anisotropy also impacts the ability of the heart to generate torsion. Cardiac fiber rearrangement associated with aging [ 44 , 53 ], pressure load hypertrophy [ 54 ], HF [ 55 ] and MI [ 22 , 23 ] lead to changes in torsion metrics. For example, during aging sub-endocardial fibers rearrange and become unable to counter the torque produced by the epicardial region.…”