A Novel Three-Dimensional Approach Towards Evaluating Endomyocardial Biopsies for Follow-Up After Heart Transplantation: X-Ray Phase Contrast Imaging and Its Agreement With Classical Histopathology

Transpl Int. 2023 Jan 24:36:11046. doi: 10.3389/ti.2023.11046. eCollection 2023.

Abstract

Endomyocardial biopsies are the gold standard for surveillance of graft rejection following heart transplantation, and are assessed by classical histopathology using a limited number of previously stained slices from several biopsies. Synchrotron propagation-based X-ray phase contrast imaging is a non-destructive method to image biological samples without tissue preparation, enabling virtual 2D and 3D histopathology. We aimed to show the feasibility of this method to assess acute cellular rejection and its agreement to classical histopathology. Right ventricular biopsies were sampled from 23 heart transplantation recipients (20 males, mean age 54±14 years) as part of standard follow-up. The clinical diagnosis of potential rejection was made using classical histopathology. One additional study sample was harvested and imaged by X-ray phase contrast imaging, producing 3D datasets with 0.65 μm pixel size, and up to 4,320 images per sample. An experienced pathologist graded both histopathological and X-ray phase contrast images in a blinded fashion. The agreement between methods was assessed by weighted kappa, showing substantial agreement (kappa up to 0.80, p < 0.01) between X-ray phase contrast imaging and classical histopathology. X-ray phase contrast imaging does not require tissue processing, allows thorough analysis of a full myocardial sample and allows identification of acute cellular rejection.

Keywords: X-ray phase contrast imaging; graft rejection; heart transplantation; histopathology; synchrotron.

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Follow-Up Studies
  • Graft Rejection / diagnostic imaging
  • Graft Rejection / pathology
  • Heart Transplantation*
  • Humans
  • Imaging, Three-Dimensional
  • Male
  • Middle Aged
  • X-Rays

Grants and funding

This project was supported by the grant #2017-303 of the Strategic Focal Area “Personalized Health and Related Technologies (PHRT)” of the ETH Domain, the Spanish Ministry of Economy and Competitiveness (grant TIN2014-52923-R, the Maria de Maeztu Units of Excellence Programme MDM-2015-0502) and Fondo Europeo de Desarrollo Regional (FEDER). This project was supported by the Scientific Support programme of the University of Zagreb for year 2018: “Analysis of myocardial structure in heart failure with X-ray phase-contrast cardiac imaging.” This project was supported by the Scientific Support programme of the University of Zagreb for year 2019: “The specificities of myocardial structure based on heart failure aetiology—an X-ray phase contrast cardiac imaging analysis.” This project was supported by the Croatian Science Foundation through the project IP-2020-02-5572 [New Paradigm in Graft Rejection Detection in Heart Transplantation Recipients: Diagnostic Utility of Synchrotron X-ray Phase Contrast Imaging (GRAFT-XPCI)].