In vivo Correlation Tensor MRI reveals microscopic kurtosis in the human brain on a clinical 3T scanner

Abstract

Diffusion MRI (dMRI) has become one of the most important imaging modalities for noninvasively probing tissue microstructure. Diffusion Kurtosis MRI (DKI) quantifies the degree of non-gaussian diffusion, which in turn has been shown to increase sensitivity towards, e.g., disease and orientation mappings in neural tissue. However, the specificity of DKI is limited as different microstructural sources can contribute to the total diffusional kurtosis, including: variance in diffusion tensor magnitudes (Kiso), variance due to intravoxel diffusion anisotropy (Kaniso), and microscopic kurtosis (K) related to restricted diffusion and/or microstructural disorder. The latter in particular is typically ignored in diffusion MRI signal modeling as it is assumed to be negligible. Recently, Correlation Tensor MRI (CTI) based on Double-Diffusion-Encoding (DDE) was introduced for kurtosis source separation and revealed non negligible K in preclinical imaging. Here, we implemented CTI for the first time on a clinical 3T scanner and investigated the kurtosis sources in healthy subjects. A robust framework for kurtosis source separation in humans is introduced, followed by estimation of the relative importance of K in the healthy brain. Using this clinical CTI approach, we find that K significantly contributes to total diffusional kurtosis both in gray and white matter tissue but, as expected, not in the ventricles. The first K maps of the human brain are presented. We find that the spatial distribution of K provides a unique source of contrast, appearing different from isotropic and anisotropic kurtosis counterparts. We further show that ignoring K - as done by many contemporary methods based on multiple gaussian component approximation for kurtosis source estimation - biases the estimation of other kurtosis sources and, perhaps even worse, compromises their interpretation. Finally, a twofold acceleration of CTI is discussed in the context of potential future clinical applications. We conclude that CTI has much potential for future in vivo microstructural characterizations in healthy and pathological tissue. HighlightsO_LICorrelation Tensor MRI (CTI) was recently proposed to resolve kurtosis sources C_LIO_LIWe implemented CTI on a 3T scanner to study kurtosis sources in the human brain C_LIO_LIIsotropic, anisotropic, and microscopic kurtosis sources were successfully resolved C_LIO_LIMicroscopic kurtosis (K) significantly contributes to overall kurtosis in human brain C_LIO_LIK provides a novel source of contrast in the human brain in vivo C_LI