The Quantification of Myocardial remodelling in a Rat Model of Myocardial Infarction by Synchrotron X-ray Phase Contrast Imaging

    Authors

    Abstract

    **Background**: Cardiac remodelling is a set of cellular, tissue and organ changes that develop as a consequence of various injuries to the heart, such as myocardial infarction (MI). Global remodelling can be assessed by echocardiography, magnetic resonance or computed tomography imaging, however combining information on both cellular and entire organ level is still not possible by currently available imaging techniques. (1, 2) A prominent technique under research is Synchrotron X-ray Phase Contrast Imaging (X-PCI) that can be used for both 3D analysis of whole hearts, as well as cardiomyocytes (CMCs) without tissue processing or destruction. In basic and translational science rodent animal models are frequently used for myocardial ischemia research. **Methods**: MI was induced by LAD ligation via a left thoracotomy in an established model of adult (8-11 week-old) Wister rats. The animals were sacrificed after 2 weeks when the hearts were extracted and imaged by X-PCI at TOMCAT beamline (Swiss Light Source, Paul Scherer Institute, Switzerland) using an energy of 20 keV with two different voxel sizes in selected regions of interest. 3D datasets obtained by this technique allowed calculation of ventricular volumes, mass and cavity dimensions, fibre orientation analysis, as well as analysis of individual cardiomyocytes (cross sectional area (CSA) calculation). We quantified global left ventricular (LV) remodelling in 4 post-MI rat hearts, and in a control healthy rat heart. In 2 post-MI hearts, the cardiomyocytes were analysed in the area of the MI (preserved cells adjacent to the fibrotic post-MI myocardium - peri-MI zone), and in the contralateral region (the non-affected myocardium). Cardiomyocytes of corresponding areas were analysed in the healthy heart alike. CSA was expressed as the mean value with standard deviation of measurements of 10 CMCs per area. **Results**: **Table 1** shows indices of global myocardial remodelling confirming wall thinning and increase in size and mass of the LV in post-MI rat hearts. The results of CSA calculations (**Table 1**) indicate significant (p2** | | | | | | | | | | **Contralateral region** | **499±141** | **477±116*** | **521±160*** | - | - | **312±62** | | **Peri-MI zone** | **737±127** | **773±118** | **701±126** | - | - | **330±92** | | | **Overall** | **321±75** | **625±194∮** | **611±168∮** | - | - | **-** | | [†] *marks significant difference in cardiomyocyte cross sectional areas between different myocardial areas in the same rat heart, while ∮ marks significant difference in cardiomyocyte cross sectional area between same myocardial areas of affected and non-affected hearts (p≤0.01). MI - myocardial infarction, LV - left ventricle **Conclusion**: X-PCI provides results consistent with previous research in the field but obtained by one single technique that proves it valuable for quantifying both global and cellular myocardial remodelling.

    Keywords

    remodelation, synchrotron, myocardial infarction, hypertrophy

    DOI

    https://doi.org/10.15836/ccar2018.433

    Literature

    1. Dejea H, Garcia-Canadilla P, Stampanoni M, Zamora M, Crispi M, Bijnens B, et al. Microstructural Analysis of Cardiac Endomyocardial Biopsies with Synchrotron Radiation-Based X-Ray Phase Contrast Imaging. In: Pop M, Wright GA. Functional Imaging and Modelling of the Heart. Cham: Springer; 2017. 23-31.
    2. Gonzalez-Tendero A, Zhang C, Balicevic V, Cárdenes R, Loncaric S, Butakoff C, et al. Whole heart detailed and quantitative anatomy, myofibre structure and vasculature from X-ray phase-contrast synchrotron radiation-based micro computed tomography. Eur Heart J Cardiovasc Imaging. 2017 Jul 1;18(7):732–41. https://doi.org/10.1093/ehjci/jew314
    Cardiologia Croatica
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    The Quantification of Myocardial remodelling in a Rat Model of Myocardial Infarction by Synchrotron X-ray Phase Contrast Imaging

    Extended Abstract
    Issue11-12
    Published
    Pages433-434
    PDF via DOIhttps://doi.org/10.15836/ccar2018.433
    remodelation
    synchrotron
    myocardial infarction
    hypertrophy

    Authors

    Ivo Planinc*ORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
    Patricia Garcia-CanadillaORCIDInstitut kardiovaskularnih znanosti, Sveučilište u Londonu, London, Ujedinjeno Kraljevstvo
    Hector DejeaORCIDPaul Scherrer Institut, Villigen, Švicarska
    Eduard GuaschORCIDOdjel kardiologije, Klinička bolnica Barcelona, Barcelona, Španjolska
    Marco StampanoniORCIDPaul Scherrer Institut, Villigen, Švicarska
    Davor MiličićORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
    Bart BijnensORCIDPhysense, DTIC, Sveučilište Pompeu Fabra, Barcelona, Španjolska
    Anne BonninORCIDPaul Scherrer Institut, Villigen, Švicarska
    Maja ČikešORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska

    *Correspondence email: ivo.planinc@gmail.com

    Abstract

    **Background**: Cardiac remodelling is a set of cellular, tissue and organ changes that develop as a consequence of various injuries to the heart, such as myocardial infarction (MI). Global remodelling can be assessed by echocardiography, magnetic resonance or computed tomography imaging, however combining information on both cellular and entire organ level is still not possible by currently available imaging techniques. (1, 2) A prominent technique under research is Synchrotron X-ray Phase Contrast Imaging (X-PCI) that can be used for both 3D analysis of whole hearts, as well as cardiomyocytes (CMCs) without tissue processing or destruction. In basic and translational science rodent animal models are frequently used for myocardial ischemia research. **Methods**: MI was induced by LAD ligation via a left thoracotomy in an established model of adult (8-11 week-old) Wister rats. The animals were sacrificed after 2 weeks when the hearts were extracted and imaged by X-PCI at TOMCAT beamline (Swiss Light Source, Paul Scherer Institute, Switzerland) using an energy of 20 keV with two different voxel sizes in selected regions of interest. 3D datasets obtained by this technique allowed calculation of ventricular volumes, mass and cavity dimensions, fibre orientation analysis, as well as analysis of individual cardiomyocytes (cross sectional area (CSA) calculation). We quantified global left ventricular (LV) remodelling in 4 post-MI rat hearts, and in a control healthy rat heart. In 2 post-MI hearts, the cardiomyocytes were analysed in the area of the MI (preserved cells adjacent to the fibrotic post-MI myocardium - peri-MI zone), and in the contralateral region (the non-affected myocardium). Cardiomyocytes of corresponding areas were analysed in the healthy heart alike. CSA was expressed as the mean value with standard deviation of measurements of 10 CMCs per area. **Results**: **Table 1** shows indices of global myocardial remodelling confirming wall thinning and increase in size and mass of the LV in post-MI rat hearts. The results of CSA calculations (**Table 1**) indicate significant (p2** | | | | | | | | | | **Contralateral region** | **499±141** | **477±116*** | **521±160*** | - | - | **312±62** | | **Peri-MI zone** | **737±127** | **773±118** | **701±126** | - | - | **330±92** | | | **Overall** | **321±75** | **625±194∮** | **611±168∮** | - | - | **-** | | [†] *marks significant difference in cardiomyocyte cross sectional areas between different myocardial areas in the same rat heart, while ∮ marks significant difference in cardiomyocyte cross sectional area between same myocardial areas of affected and non-affected hearts (p≤0.01). MI - myocardial infarction, LV - left ventricle **Conclusion**: X-PCI provides results consistent with previous research in the field but obtained by one single technique that proves it valuable for quantifying both global and cellular myocardial remodelling.

    Literature

    1. 1.
      Dejea H, Garcia-Canadilla P, Stampanoni M, Zamora M, Crispi M, Bijnens B, et al. Microstructural Analysis of Cardiac Endomyocardial Biopsies with Synchrotron Radiation-Based X-Ray Phase Contrast Imaging. In: Pop M, Wright GA. Functional Imaging and Modelling of the Heart. Cham: Springer; 2017. 23-31.
    2. 2.
      Gonzalez-Tendero A, Zhang C, Balicevic V, Cárdenes R, Loncaric S, Butakoff C, et al. Whole heart detailed and quantitative anatomy, myofibre structure and vasculature from X-ray phase-contrast synchrotron radiation-based micro computed tomography. Eur Heart J Cardiovasc Imaging. 2017 Jul 1;18(7):732–41.DOI