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

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.

Etiology-Discriminative Multimodal Imaging of Left Ventricular Hypertrophy and Synchrotron-Based Assessment of Microstructural Tissue Remodeling.

Background: Distinguishing the etiology of left ventricular hypertrophy (LVH) is clinically relevant due to patient outcomes and management. Easily obtained, echocardiography-based myocardial deformation patterns may improve standard non-invasive phenotyping, however, the relationship between deformation phenotypes and etiology-related, microstructural cardiac remodeling has not been reported. Synchrotron radiation-based X-ray phase-contrast imaging (X-PCI) can provide high resolution, three-dimensional (3D) information on myocardial microstructure. The aim of this pilot study is to apply a multiscale, multimodality protocol in LVH patients undergoing septal myectomy to visualize in vivo and ex vivo myocardial tissue and relate non-invasive LVH imaging phenotypes to the underlying synchrotron-assessed microstructure. Methods and findings: Three patients (P1-3) undergoing septal myectomy were comprehensively studied. Medical history was collected, and patients were imaged with echocardiography/cardiac magnetic resonance prior to the procedure. Myocardial tissue samples obtained during the myectomy were imaged with X-PCI generating high spatial resolution images (0.65 µm) to assess myocyte organization, 3D connective tissue distribution and vasculature remodeling. Etiology-centered non-invasive imaging phenotypes, based on findings of hypertrophy and late gadolinium enhancement (LGE) distribution, and enriched by speckle-tracking and tissue Doppler echocardiography deformation patterns, identified a clear phenotype of hypertensive heart disease (HTN) in P1, and hypertrophic cardiomyopathy (HCM) in P2/P3. X-PCI showed extensive interstitial fibrosis with normal 3D myocyte and collagen organization in P1. In comparison, in P2/P3, X-PCI showed 3D myocyte and collagen disarray, as well as arterial wall hypertrophy with increased perivascular collagen, compatible with sarcomere-mutation HCM in both patients. The results of this pilot study suggest the association of non-invasive deformation phenotypes with etiology-related myocyte and connective tissue matrix disorganization. A larger patient cohort could enable statistical analysis of group characteristics and the assessment of deformation pattern reproducibility. Conclusion: High-resolution, 3D X-PCI provides novel ways to visualize myocardial remodeling in LVH, and illustrates the correspondence of macrostructural and functional non-invasive phenotypes with invasive microstructural phenotypes, suggesting the potential clinical utility of non-invasive myocardial deformation patterns in phenotyping LVH in everyday clinical practice.

Micro-computed tomography (micro-CT) for the assessment of myocardial disarray, fibrosis and ventricular mass in a feline model of hypertrophic cardiomyopathy.

Micro-computed tomography (micro-CT) is a high-resolution imaging modality that provides accurate tissue characterization. Hypertrophic cardiomyopathy (HCM) occurs as a spontaneous disease in cats, and is characterized by myocardial hypertrophy, disarray and fibrosis, as in humans. While hypertrophy/mass (LVM) can be objectively measured, fibrosis and myocyte disarray are difficult to assess. We evaluated the accuracy of micro-CT for detection and quantification of myocardial disarray and fibrosis by direct comparison with histopathology. 29 cat hearts (12 normal and 17 HCM hearts) underwent micro-CT and pathologic examination. Myocyte orientation was assessed using structure tensor analysis by determination of helical angle (HA), fractional anisotropy (FA) and myocardial disarray index (MDI). Fibrosis was segmented and quantified based on comparison of gray-scale values in normal and fibrotic myocardium. LVM was obtained by determining myocardial volume. Myocardial segments with low FA, low MDI and disruption of normal HA transmural profile on micro-CT were associated with myocardial disarray on histopathology. FA was consistently lower in HCM than normal hearts. Assessment of fibrosis on micro-CT closely matched the histopathologic evaluation. LVM determined by micro-CT was higher in HCM than normal hearts. Micro-CT can be used to detect and quantify myocardial disarray and fibrosis and determine myocardial mass in HCM.