Synchrotron-based X-ray phase contrast imaging of transmural cardiac tissue in patients treated for advanced heart failure

    Authors

    Keywords

    cardiomyopathy, left ventricular assist device implantation, heart transplantation, synchrotron imaging, collagen segmentation

    DOI

    https://doi.org/10.15836/ccar2022.263

    Full Text

    **Background:** Cardiac imaging is essential in identifying structural changes in advanced heart failure (HF) enabling understanding of the underlying pathophysiology. Synchrotron radiation-based X-ray phase contrast imaging (X-PCI) is a novel non-destructive imaging modality that can provide high resolution three-dimensional (3D) visualization of cardiac tissue on the macro- and microstructural level, enabling analysis from the epi- to the endocardium, as well as collagen matrix reconstruction (1, 2). We aimed to explore the feasibility of utilising X-PCI for the imaging of full thickness myocardial samples and to explore microstructural features of cardiac tissue in different advanced HF aetiologies. **Patients and Methods:** Eight patients were included - two receiving a left ventricular assist device (LVAD) (LVAD group), and six undergoing heart transplantation (HTx) (HTx group). Aetiology of advanced HF in the LVAD group was ischaemic heart disease (IHD) and dilated cardiomyopathy (DCM). In the HTx group, 2 patients had IHD, while one patient had each of the following: DCM, restrictive cardiomyopathy, toxic cardiomyopathy, and adult congenital heart disease. Transmural tissue samples were obtained by left ventricular apical coring (LVAD group) and from the explanted hearts (HTx group). The tissue specimens were imaged by X-PCI at the Paul Scherrer Institute (Villigen, Switzerland) using a multi-scale setup resulting in low (LR) and high resolution (HR) imaging, at 5.8 and 0.65 µm effective pixel size, respectively. Imaging datasets were used to visualize morphological features and an open-source software (Ilastik) was used for semi-automatic collagen segmentation. **Results:** The images resulting from the apical coring samples are shown in **Figure 1****.** X-PCI enabled multiscale exploration of transmural myocardial tissue samples providing 3D virtual histopathology. Additionally, reconstruction of the collagen matrix highlighting microstructural features and potential differences amongst different aetiologies of advanced HF was shown to be feasible without further sample preparation. FIGURE 1. Examples of X-ray phase contrast imaging images of different aetiologies of advanced heart failure in the left ventricular assist device group (dilated cardiomyopathy – panels A, B, C; ischaemic cardiomyopathy – panels D, E, F). Panels A and D show low resolution images, B and E high resolution images, and C and F show collagen segmentation. **Conclusion:** X-PCI is a non-destructive, 3D imaging method that can extend the amount of information available from ex-vivo tissue analysis and potentially improve disease phenotyping.

    Literature

    1. Dejea H, Garcia-Canadilla P, Cook AC, Guasch E, Zamora M, Crispi F, et al. Comprehensive Analysis of Animal Models of Cardiovascular Disease using Multiscale X-Ray Phase Contrast Tomography. Sci Rep. 2019 May 6;9(1):6996. https://doi.org/10.1038/s41598-019-43407-z
    2. Loncaric F, Garcia-Canadilla P, Garcia-Alvarez A, Sanchis L, Prat S, Doltra A, et al. Etiology-Discriminative Multimodal Imaging of Left Ventricular Hypertrophy and Synchrotron-Based Assessment of Microstructural Tissue Remodeling. Front Cardiovasc Med. 2021 May 25;8:670734. https://doi.org/10.3389/fcvm.2021.670734
    Cardiologia Croatica
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    Synchrotron-based X-ray phase contrast imaging of transmural cardiac tissue in patients treated for advanced heart failure

    Extended Abstract
    Issue9-10
    Published
    Pages263-264
    PDF via DOIhttps://doi.org/10.15836/ccar2022.263
    cardiomyopathy
    left ventricular assist device implantation
    heart transplantation
    synchrotron imaging
    collagen segmentation

    Authors

    Nikola Škreb*ORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Filip LončarićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Anne BonninORCIDPaul Scherrer Institute, Villigen, Switzerland
    Hector DejeaORCIDLund University, Lund, Sweden
    Ivana IlićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Antonio HanžekORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Hrvoje GašparovićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Davor MiličićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Ivo PlanincORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Maja ČikešORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia

    *Correspondence email: nikola.skreb7@gmail.com

    Full Text

    Background: Cardiac imaging is essential in identifying structural changes in advanced heart failure (HF) enabling understanding of the underlying pathophysiology. Synchrotron radiation-based X-ray phase contrast imaging (X-PCI) is a novel non-destructive imaging modality that can provide high resolution three-dimensional (3D) visualization of cardiac tissue on the macro- and microstructural level, enabling analysis from the epi- to the endocardium, as well as collagen matrix reconstruction (1, 2). We aimed to explore the feasibility of utilising X-PCI for the imaging of full thickness myocardial samples and to explore microstructural features of cardiac tissue in different advanced HF aetiologies.

    Patients and Methods: Eight patients were included - two receiving a left ventricular assist device (LVAD) (LVAD group), and six undergoing heart transplantation (HTx) (HTx group). Aetiology of advanced HF in the LVAD group was ischaemic heart disease (IHD) and dilated cardiomyopathy (DCM). In the HTx group, 2 patients had IHD, while one patient had each of the following: DCM, restrictive cardiomyopathy, toxic cardiomyopathy, and adult congenital heart disease. Transmural tissue samples were obtained by left ventricular apical coring (LVAD group) and from the explanted hearts (HTx group). The tissue specimens were imaged by X-PCI at the Paul Scherrer Institute (Villigen, Switzerland) using a multi-scale setup resulting in low (LR) and high resolution (HR) imaging, at 5.8 and 0.65 µm effective pixel size, respectively. Imaging datasets were used to visualize morphological features and an open-source software (Ilastik) was used for semi-automatic collagen segmentation.

    Results: The images resulting from the apical coring samples are shown in Figure 1. X-PCI enabled multiscale exploration of transmural myocardial tissue samples providing 3D virtual histopathology. Additionally, reconstruction of the collagen matrix highlighting microstructural features and potential differences amongst different aetiologies of advanced HF was shown to be feasible without further sample preparation.

    FIGURE 1. Examples of X-ray phase contrast imaging images of different aetiologies of advanced heart failure in the left ventricular assist device group (dilated cardiomyopathy – panels A, B, C; ischaemic cardiomyopathy – panels D, E, F). Panels A and D show low resolution images, B and E high resolution images, and C and F show collagen segmentation.

    Conclusion: X-PCI is a non-destructive, 3D imaging method that can extend the amount of information available from ex-vivo tissue analysis and potentially improve disease phenotyping.

    Literature

    1. 1.
      Dejea H, Garcia-Canadilla P, Cook AC, Guasch E, Zamora M, Crispi F, et al. Comprehensive Analysis of Animal Models of Cardiovascular Disease using Multiscale X-Ray Phase Contrast Tomography. Sci Rep. 2019 May 6;9(1):6996.DOI
    2. 2.
      Loncaric F, Garcia-Canadilla P, Garcia-Alvarez A, Sanchis L, Prat S, Doltra A, et al. Etiology-Discriminative Multimodal Imaging of Left Ventricular Hypertrophy and Synchrotron-Based Assessment of Microstructural Tissue Remodeling. Front Cardiovasc Med. 2021 May 25;8:670734.DOI