Myocardial mesostructure and mesofunction

Abstract

The complex and highly organized structural arrangement of some five billion cardiomyocytes directs the coordinated electrical activity and mechanical contraction of the human heart. The characteristic transmural change in cardiomyocyte orientation underlies base-to-apex shortening, circumferential shortening, and left ventricular torsion during contraction. Individual cardiomyocytes shorten approximately 15% and increase in diameter approximately 8%. Remarkably, however, the left ventricular wall thickens by up to 30-40%. To accommodate this, the myocardium must undergo significant structural rearrangement during contraction. At the mesoscale, collections of cardiomyocytes are organized into sheetlets, and sheetlet shear is the fundamental mechanism of rearrangement that produces wall thickening. Herein we review the histological and physiological studies of myocardial mesostructure that have established the sheetlet shear model of wall thickening. Recent developments in tissue clearing techniques allow for imaging of whole hearts at the cellular scale, while magnetic resonance imaging (MRI) and computed tomography (CT) can image the myocardium at the mesoscale (tens to hundreds of microns) to resolve cardiomyocyte orientation and organization. Through histology, cardiac diffusion tensor imaging (cDTI) and other modalities, mesostructural sheetlets have been confirmed in both animal and human hearts. Recent in vivo cDTI methods have measured reorientation of sheetlets during the cardiac cycle. We also examine the role of pathological cardiac remodeling on sheetlet organization and reorientation, and the impact this has on ventricular function and dysfunction. We also review the unresolved mesostructural questions and challenges that may direct future work in the field.

Collagenase treatment reduces the anisotropy of ultrasonic backscatter in rat myocardium by reducing collagen crosslinks

“…Efforts are being made to use ultrasonic backscatter to understand collagen content in patients (Hoyt et al, 1984;O'Donnell et al, 1981;Rijsterborgh et al, 1996;Zaidman et al, 2008), but were limited to a specific myocardial position. Myofiber architecture and mesostructure of the heart are gaining interest, especially when applied to MRI (Wilson et al, 2022). Our previous studies have suggested that the myofiber architecture in the heart could be determined using ultrasonic backscatter (Milne et al, 2012(Milne et al, , 2016(Milne et al, , 2019, but it was unclear whether collagen or muscle was a primary determinant of this measure.…”

Diffusion Tensor Phenomapping of the Healthy and Pressure-Overloaded Human Heart

“…1i) and consistently showed the expected evoluJon in HA from the endo to epicardium. [1][2][3][4][5] To evaluate the impact of the improved resoluJon, 3-5 HA maps at the midventricular level were selected in each subject (n=8) and downsampled to the standard (2.5mm) resoluJon. In each subject, the values in the selected slices were combined to yield a single value for that subject.…”

“…Diffusion tensor MRI (DTI) of the heart allows the microstructure of the myocardium, which varies markedly from endocardium to epicardium, to be measured noninvasively. [1][2][3][4][5] However, the resoluJon of most translaJonal DTI techniques provides only 4-5 voxels across the myocardium without interpolaJon, [6][7][8][9][10] which likely under-resolves important features. Here, we present an approach to improve the spaJal resoluJon of cardiac DTI by almost 10-fold.…”

Effects of myocardial sheetlet sliding on left ventricular function

“…Recent histology studies revealed that the LV myocytes are organized into laminar microstructures, which were given the term sheetlets, and were about three to six myocytes in thickness (LeGrice et al 1995 ; Wilson et al 2022 ). Diffusion tensor cardiac magnetic resonance imaging (DTCMR) further revealed that these sheetlets have specific systolic–diastolic dynamics, where the sheetlet angle or orientation experiences a cyclic tilt away from the LV wall plane during systolic contraction (Ferreira et al 2014 ; Nielles-Vallespin et al 2017 ).…”