title: Validation of diffusion tensor MRI measurements of cardiac microstructure with structure tensor synchrotron radiation imaging.
abstract: BACKGROUND
  Diffusion tensor imaging (DTI) is widely used to assess tissue microstructure non-invasively. Cardiac DTI enables inference of cell and sheetlet orientations, which are altered under pathological conditions. However, DTI is affected by many factors, therefore robust validation is critical. Existing histological validation is intrinsically flawed, since it requires further tissue processing leading to sample distortion, is routinely limited in field-of-view and requires reconstruction of three-dimensional volumes from two-dimensional images. In contrast, synchrotron radiation imaging (SRI) data enables imaging of the heart in 3D without further preparation following DTI. The objective of the study was to validate DTI measurements based on structure tensor analysis of SRI data.
  
  
  METHODS
  One isolated, fixed rat heart was imaged ex vivo with DTI and X-ray phase contrast SRI, and reconstructed at 100 μm and 3.6 μm isotropic resolution respectively. Structure tensors were determined from the SRI data and registered to the DTI data.
  
  
  RESULTS
  Excellent agreement in helix angles (HA) and transverse angles (TA) was observed between the DTI and structure tensor synchrotron radiation imaging (STSRI) data, where HADTI-STSRI= -1.4° ± 23.2° and TADTI-STSRI= -1.4° ± 35.0° (mean ± 1.96 standard deviation across all voxels in the left ventricle). STSRI confirmed that the primary eigenvector of the diffusion tensor corresponds with the cardiomyocyte long-axis across the whole myocardium.
  
  
  CONCLUSIONS
  We have used STSRI as a novel and high-resolution gold standard for the validation of DTI, allowing like-with-like comparison of three-dimensional tissue structures in the same intact heart free of distortion. This represents a critical step forward in independently verifying the structural basis and informing the interpretation of cardiac DTI data, thereby supporting the further development and adoption of DTI in structure-based electro-mechanical modelling and routine clinical applications.
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.|Leeds Institute of Cardiovascular & Metabolic Medicine, University of Leeds, Leeds, UK.
authors.forename: Irvin
authors.initials: I
authors.lastname: Teh
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Darryl
authors.initials: D
authors.lastname: McClymont
authors.affiliation: Diamond Light Source, Didcot, UK.|Department of Physics and Astronomy, University College London, London, UK.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Zdora
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Whittington
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London, London, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Davidoiu
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London, London, UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Lygate
authors.affiliation: Diamond Light Source, Didcot, UK.|University of Manchester, Manchester, UK.|Feinberg School of Medicine, Northwestern University, Chicago, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Rau
authors.affiliation: Diamond Light Source, Didcot, UK.
authors.forename: Irene
authors.initials: I
authors.lastname: Zanette
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. jurgen.schneider@cardiov.ox.ac.uk.|Leeds Institute of Cardiovascular & Metabolic Medicine, University of Leeds, Leeds, UK. jurgen.schneider@cardiov.ox.ac.uk.
authors.forename: Jürgen E
authors.initials: JE
authors.lastname: Schneider
mesh_terms: D000818:Animals; D003198:Computer Simulation; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging*; D007090:Image Interpretation, Computer-Assisted; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac; D011237:Predictive Value of Tests; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D017356:Synchrotrons
keywords: Cardiovascular magnetic resonance; Diffusion tensor imaging; Structure tensor; Synchrotron radiation imaging; Tissue microstructure; Validation