Abstract

Measurements of water diffusion with MRI have been used as a biomarker of tissue microstructure and heterogeneity. In this study, diffusion kurtosis tensor imaging (DKTI) of the brain was undertaken in 10 healthy volunteers at a clinical field strength of 3 T. Diffusion and kurtosis metrics were measured in regions-of-interest on the resulting maps and compared with quantitative analysis of normal post-mortem tissue histology from separate age-matched donors. White matter regions showed low diffusion (0.60 ± 0.04 × 10–3 mm2/s) and high kurtosis (1.17 ± 0.06), consistent with a structured heterogeneous environment comprising parallel neuronal fibres. Grey matter showed intermediate diffusion (0.80 ± 0.02 × 10–3 mm2/s) and kurtosis (0.82 ± 0.05) values. An important finding is that the subcortical regions investigated (thalamus, caudate and putamen) showed similar diffusion and kurtosis properties to white matter. Histological staining of the subcortical nuclei demonstrated that the predominant grey matter was permeated by small white matter bundles, which could account for the similar kurtosis to white matter. Quantitative histological analysis demonstrated higher mean tissue kurtosis and vector standard deviation values for white matter (1.08 and 0.81) compared to the subcortical regions (0.34 and 0.59). Mean diffusion on DKTI was positively correlated with tissue kurtosis (r = 0.82, p < 0.05) and negatively correlated with vector standard deviation (r = -0.69, p < 0.05). This study demonstrates how DKTI can be used to study regional structural variations in the cerebral tissue microenvironment and could be used to probe microstructural changes within diseased tissue in the future.

Highlights

  • Measurements of water diffusion with magnetic resonance imaging (MRI) have been used as a biomarker of tissue microstructure and heterogeneity

  • Axial and radial diffusion were significantly higher in the cerebrospinal fluid (CSF) (1.42 ± 0.03, 1.67 ± 0.04 and 1.43 ± 0.05 × 1­ 0–3 ­mm2/s) compared to white matter (WM) (0.66 ± 0.01, 1.10 ± 0.01 and 0.50 ± 0.01 × ­10–3 ­mm2/s; p < 0.05) and grey matter (GM) (0.81 ± 0.02, 0.99 ± 0.01 and 0.73 ± 0.01 × ­10–3 ­mm2/s; p < 0.05)

  • fractional anisotropy (FA) was significantly higher in WM (0.51 ± 0.01) compared to GM (0.21 ± 0.00; p < 0.05) and CSF (0.12 ± 0.01; p < 0.05), while Kurtosis fractional anisotropy (KFA) was higher in WM (0.64 ± 0.02) compared to GM (0.51 ± 0.02; p < 0.05) and CSF (0.23 ± 0.01; p < 0.05)

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Summary

Introduction

Measurements of water diffusion with MRI have been used as a biomarker of tissue microstructure and heterogeneity. Quantitative histological analysis demonstrated higher mean tissue kurtosis and vector standard deviation values for white matter (1.08 and 0.81) compared to the subcortical regions (0.34 and 0.59). Imaging biomarkers of tissue microstructure and heterogeneity are clinically important and several have found a role in routine clinical practice, such as the use of water diffusion measurements using magnetic resonance imaging (MRI). The non-invasive imaging of such biomarkers has the potential to: characterise tumours and assess grade without the need for a biopsy, enabling earlier monitoring of disease progression and treatment response; and guide clinical management by facilitating patient ­stratification[1] These biomarkers have diagnostic and prognostic use in assessing the structural changes seen in other disease processes, such as ischaemia, demyelination or n­ eurodegeneration[2]. Microstructure diffusion methods attempt to overcome this limitation but make a number of assumptions regarding the underlying geometrical properties of the t­issue[8,9]

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