Evidence for microscopic kurtosis in neural tissue revealed by correlation tensor MRI

Purpose: The impact of microscopic diffusional kurtosis (mu K), arising from restricted diffusion and/or structural disorder, remains a controversial issue in contemporary diffusion MRI (dMRI). Recently, correlation tensor imaging (CTI) was introduced to disentangle the sources contributing to diffusional kurtosis, without relying on a-priori multi-gaussian component (MGC) or other microstructural assumptions. Here, we investigated mu K in in vivo rat brains and assessed its impact on state-of-the-art methods ignoring mu K. Theory and Methods: CTI harnesses double diffusion encoding (DDE) experiments, which were here improved for speed and minimal bias using four different sets of acquisition parameters. The robustness of the improved CTI protocol was assessed via simulations. In vivo CTI acquisitions were performed in healthy rat brains using a 9.4T pre-clinical scanner equipped with a cryogenic coil, and targeted the estimation of mu K, anisotropic kurtosis, and isotropic kurtosis. Results: The improved CTI acquisition scheme substantially reduces scan time and importantly, also minimizes higher-order-term biases, thus enabling robust mu K estimation, alongside K-aniso and K-iso metrics. Our CTI experiments revealed positive mu K both in white and gray matter of the rat brain in vivo; mu K is the dominant kurtosis source in healthy gray matter tissue. The non-negligible mu K substantially were found to bias prior MGC analyses of K-iso and K-aniso. Conclusions: Correlation Tensor MRI offers a more accurate and robust characterization of kurtosis sources than its predecessors. mu K is non-negligible in vivo in healthy white and gray matter tissues and could be an important biomarker for future studies. Our findings thus have both theoretical and practical implications for future dMRI research.

Automated summary

Correlation tensor imaging (CTI) with improved double diffusion encoding experiments estimated microscopic diffusional kurtosis (mu K) in in vivo rat brains, showing mu K is a dominant kurtosis source in healthy white and gray matter tissues and can bias prior multi-gaussian component analyses.