Multi-scale analysis of cardiac myoarchitecture

Abstract

The distribution and generation of force within the myocardium during normal contractility is dictated by the tissue's underlying 3D myoarchitecture. The presence of disordered myoarchitecture may in turn constitute the pathological basis of impaired cardiac mechanics in numerous clinical conditions, such as the remodeling heart following myocardial infarction and cardiomyopathies. To investigate the multi-scale nature of architectural disarray in the setting of myocardial disease, a dual imaging approach consisting of diffusion spectrum magnetic resonance imaging (DSI) and high-speed multislice two-photon microscopy (TPM) was used. DSI is a technique that derives fiber orientation from directionality of proton diffusion, whereas TPM derives cellular alignment from an autocorrelation of 3D resolved images of cells and subcellular structure. Mesoscale tract representations of myofiber orientation are generated from similarly aligned diffusion or autocorrelation vectors. These methods were applied to study induced myocardial infarction in the rat and hypertrophic cardiomyopathy associated with deletion of the gene for myosin binding protein C (cMyBP-C) in the mouse. Normal cardiac muscle fiber alignment within the ventricular wall was characterized by a series of helical tracts transitioning from a lefthanded orientation in the subepicardium to circumferential in the mid-myocardium to righthanded in the subendocardium. Infarcted hearts displayed a fiber void in the infarct zone and an extension of both subepicardial and subendocardial fibers beyond the border zone. It's hypothesized that the growth of fibers contributes to the remodeling process and provides tensile strength to the myocardium during contraction.

(cont.) The hearts obtained from the cMyBP-C knockouts displayed significant myoarchitectural disarray characterized by a loss of voxel to voxel orientational coherence for fibers located from the mid-myocardium to subendocardium, resulting in a change in the transmural progression of remaining helical fibers. These observations suggest an association between cMyBP-C expression and cardiac fiber alignment, where variations in torsional rotation may constitute a mechanism for pump failure in hypertrophic cardiomyopathy. These results substantiate the use of multi-scale imaging methods to enhance understanding of molecular and cellular contributions to tissue mechanical function.