Comprehensive assessment of myocardial remodeling in ischemic heart disease by synchrotron propagation based X-ray phase contrast imaging

Abstract

Cardiovascular research is in an ongoing quest for a superior imaging method to integrate gross-anatomical information with microanatomy, combined with quantifiable parameters of cardiac structure. In recent years, synchrotron radiation-based X-ray Phase Contrast Imaging (X-PCI) has been extensively used to characterize soft tissue in detail. The objective was to use X-PCI to comprehensively quantify ischemic remodeling of different myocardial structures, from cell to organ level, in a rat model of myocardial infarction. Myocardial infarction-induced remodeling was recreated in a well-established rodent model. Ex vivo rodent hearts were imaged by propagation based X-PCI using two configurations resulting in 5.8 µm and 0.65 µm effective pixel size images. The acquired datasets were used for a comprehensive assessment of macrostructural changes including the whole heart and vascular tree morphology, and quantification of left ventricular myocardial thickness, mass, volume, and organization. On the meso-scale, tissue characteristics were explored and compared with histopathological methods, while microstructural changes were quantified by segmentation of cardiomyocytes and calculation of cross-sectional areas. Propagation based X-PCI provides detailed visualization and quantification of morphological changes on whole organ, tissue, vascular as well as individual cellular level of the ex vivo heart, with a single, non-destructive 3D imaging modality.

Detailed quantification of cardiac ventricular myocardial architecture in the embryonic and fetal mouse heart by application of structure tensor analysis to high resolution episcopic microscopic data

“…We have previously demonstrated that MDI, a parameter that quantifies the similarity in the alignment of myocytes within an ROI, is a good descriptor of myocardial disarray/disorganisation ( Garcia-Canadilla et al, 2019 ; Novo Matos et al, 2020 ; Planinc et al, 2021 ). In this work, we have shown that MDI increases gradually with gestational age in both ventricles, indicative of the increasing organisation of the ventricles with development, as illustrated also in Figure 8 .…”

Multiscale X-ray Structural Analysis of Cardiac Cells and Tissues

“…al. [197], we investigated structural changes caused by cardiovascular and genetic pathologies in hydrated conditions. Datasets of entire murine hearts were acquired at a voxelsize of 2.8 µm and regions of interest were probed at 650 nm voxelsize.…”

“…this approach, studies on the influence of cardiovascular disease in mouse models were performed [181,197]. Besides differences in fiber orientation, the wall thickness of the myocardium was analyzed and a few single cardiomyocytes were manually segmented.…”

Preparation of large biological samples for high-resolution, hierarchical, multi-modal imaging

“…Synchrotron X-ray tomography (sCT) has proved to be one of the most powerful X-ray-based imaging techniques due to its high brightness 19 , enabling the observation of soft tissue at high resolution, with enough contrast to see the structural components [20][21][22] . In particular, phase-contrast-based sCT 23 , combined with the right sample preparation and mounting procedure has provided extensive information on biological tissues such as heart fibre orientation 24,25 or brain cellular map 26 . Phase-contrast enables visualisation of soft tissues that would be invisible with conventional X-ray tomography without the use of a contrast agent 27 .…”