Investigating the relationship between diffusion kurtosis tensor imaging (DKTI) and histology within the normal human brain

Funder: CRUK and EPSRC Cancer Imaging Centre in Cambridge and Manchester; doi: http://dx.doi.org/10.13039/501100014679Funder: Engineering and Physical Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000266Funder: CRUK Cambridge CentreFunder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; doi: http://dx.doi.org/10.13039/501100002927Funder: National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre (BRC)Funder: Experimental Cancer Medicine Centre (ECMC)Funder: The Lundbeck FoundationFunder: Evelyn Trust; doi: http://dx.doi.org/10.13039/501100004282Funder: Mark Foundation for Integrative Cancer ResearchAbstract: 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