Abstract

BackgroundDiffusion 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.MethodsOne 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.ResultsExcellent 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.ConclusionsWe 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.

Highlights

  • Diffusion tensor imaging (DTI) is widely used to assess tissue microstructure non-invasively

  • Residual low-frequency banding artefacts are observed in the synchrotron radiation imaging (SRI) data, these occur on a greater length scale than the structure tensor (ST) convolution kernel, and have little impact on estimation of the ST

  • The key criteria for validating DTI for assessment of tissue microstructure are that (i) cellular structures can be resolved in three dimensions, (ii) the sample is imaged with both modalities in the same physical state and (iii) validation can be performed in the whole organ

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Summary

Introduction

Diffusion tensor imaging (DTI) is widely used to assess tissue microstructure non-invasively. Diffusion magnetic resonance imaging (MRI) [1] is a valuable method for characterising the three-dimensional (3D) microstructure in biological tissues It is finding increasing application in the heart, and has been used to assess cardiac hypertrophy [2,3,4], myocardial infarction [5, 6], myocardial fibrosis [7], cardiac contraction [8,9,10] and inform on patient-specific tissue mechanical properties [11]. Recent in vivo cardiac DTI in rats [15] and humans [16] employed resolutions of 0.35 × 0.35 × 3 mm and 2.8 × 2.8 × 8 mm respectively This translates to averaging over large numbers of cardiomyocytes within each voxel, on the order of 1 × 104 and 1 × 106 respectively, based on histological measurements [17,18,19]. In fitting a single tensor to the DTI data, the structural complexity of the myocardium within each voxel, comprising multiple cell types and orientations, is considerably reduced into three orthogonal eigenvectors and eigenvalues, that assumes unrestricted diffusion in a single compartment

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