A high-resolution cardiovascular magnetic resonance diffusion tensor map from ex-vivo C57BL/6 murine hearts

Abstract

BackgroundThe 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).MethodsImaging 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.ResultsResults 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 × 10−4 mm2/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.ConclusionsThis 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.

Biomimetic phantom for cardiac diffusion MRI

“…Larger pore sizes relative to a previous study were specified to account for the higher ADC and lower FA in cardiac tissue relative to brain white matter. 12 We report values comparable to ex vivo mouse and rat cardiac data reported in the literature, where mean ADC ranged from 0.57-0.89 3 10 -3 mm 2 /s, and FA ranged from 0.25-0.40, 16,17 and show the stability of these measurements over 4 months. 18 We assessed the geometry of the fiber strips based on their nominal thickness and measured mean helix angle, and found that the effective radii of curvature of the inner, middle, and outer strips were 273 mm, 4.88 mm, and 526 mm, respectively.…”

“…Examples include high-resolution DTI in mouse hearts. 17 and diffusion spectrum imaging in infarcted rat hearts 20 The design of a phantom needs to balance mimicking biological structure, reproducibility in manufacture, and amenability to characterization and validation. On the one hand, it could be argued that the phantom should recapitulate the branching syncytium and discrete sheet arrangement found in the myocardium.…”

Imaging technologies for cardiac fiber and heart failure: a review

“…1. The complex structural organization of cardiac fibers and the spatial arrangement of cardiomyocytes in laminar sheetlets significantly contribute to cardiac function and contractile ejection patterns [14]. Indirect estimation of local cardiac fiber orientation using the procedure of mapping the cardiac fiber from DTI data has been done by MRI and ultrasound [16, 46, 47].…”

“…Some animal models that have been used with these imaging protocols for HF studies are rat [76, 77], canine [2, 10, 50, 78, 79], rabbit [12, 80], pig [81], sheep [56, 80, 82], and mice [14, 83]. Figure 3 shows representative DT-MRI images of hearts from a mouse, a rabbit, and a sheep.…”

“…The cardiac fibers or cardiac myofibers form a complex, three-dimensional network that is packed with contractile elements. Orientation of cardiac fibers has an important role in determining the LV pump function [14, 15] and cardiac electrophysiological and mechanical properties [16–19], both of which make it critical in the study of heart failure (HF). Advances in high-resolution imaging and improvements in image registration make it easier to identify changes in cardiac microstructures.…”