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.
Highlights
While ischemic heart disease is one of the most studied cardiac pathologies, many questions remain regarding the understanding of myocardial remodeling with improved treatment and more tissue salvage as the ultimate goal
We present a comprehensive assessment of the macro, meso, and microstructural changes caused by myocardial infarction (MI) in an ex vivo rat model of left coronary artery ligation
The entirety of information gained by propagation based (PB) X-ray Phase Contrast Imaging (X-PCI) in an animal model of ischemic heart disease would conventionally require using several different imaging modalities in conjunction with histopathological analysis
Summary
While ischemic heart disease is one of the most studied cardiac pathologies, many questions remain regarding the understanding of myocardial remodeling with improved treatment and more tissue salvage as the ultimate goal. To develop protective or tissue repair strategies, the in-depth understanding of the underlying pathophysiological processes and the involved structural changes of the heart are of paramount importance This is amalgamated in an imaging modality enabling the integration of structural information from cell to organ level. Cardiac remodeling is a combined response of cardiomyocytes and other cells, myocardial tissue, and the heart as an organ, to different adverse pathophysiological processes (such as loss of contractile force by necrosis or apoptosis of cardiomyocytes, cellular hypertrophy, intercellular matrix changes like fibrosis, or deposition of different metabolic end-products)[1]. In the cardiovascular field, X-PCI has so far been utilized for ex vivo imaging of animal models, human fetus hearts and transmural samples of adult human hearts, both normal and d iseased[6,7,8,9,10,11,12,13,14,15,16]
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