A method to remove the influence of fixative concentration on postmortem T-2 maps using a kinetic tensor model

Formalin fixation has been shown to substantially reduce T-2 estimates, primarily driven by the presence of fixative in tissue. Prior to scanning, post-mortem samples are often placed into a fluid that has more favourable imaging properties. This study investigates whether there is evidence for a change in T-2 in regions close to the tissue surface due to fixative outflux into this surrounding fluid. Furthermore, we investigate whether a simulated spatial map of fixative concentration can be used as a confound regressor to reduce T-2 inhomogeneity. To achieve this, T-2 maps and diffusion tensor estimates were obtained in 14 whole, formalin-fixed post-mortem brains placed in Fluorinert approximately 48 hr prior to scanning. Seven brains were fixed with 10% formalin and seven brains were fixed with 10% neutral buffered formalin (NBF). Fixative outflux was modelled using a proposed kinetic tensor (KT) model, which incorporates voxelwise diffusion tensor estimates to account for diffusion anisotropy and tissue-specific diffusion coefficients. Brains fixed with 10% NBF revealed a spatial T-2 pattern consistent with modelled fixative outflux. Confound regression of fixative concentration reduced T-2 inhomogeneity across both white and grey matter, with the greatest reduction attributed to the KT model versus simpler models of fixative outflux. No such effect was observed in brains fixed with 10% formalin. Correlations between the transverse relaxation rate R-2 and ferritin/myelin proteolipid protein (PLP) histology lead to an increased similarity for the relationship between R-2 and PLP for the two fixative types after KT correction.