Abstract Formalin fixation has been shown to substantially reduce T 2 estimates when performing post-mortem imaging, primarily driven by the presence of bulk fixative in tissue. Prior to scanning, post-mortem tissue samples are often placed into a fluid that has more favourable imaging properties, such as matched magnetic susceptibility. This study investigates whether there is any evidence for a change in T 2 in regions close to the tissue surface in post-mortem T 2 maps 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 hours prior to scanning. This consisted of 7 brains fixed with 10% formalin and 7 brains fixed with 10% neutral buffered formalin (NBF). Fixative outflux was modelled using a 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 the 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 vs simpler models of fixative outflux. No such effect was observed in brains fixed with 10% formalin. Correlations with ferritin and myelin proteolipid protein (PLP) histology lead to an increased similarity for the relationship between T 2 and PLP for the two fixative types after KT correction. Only small correlations were identified between T 2 and ferritin before and after KT correction.

A method to remove the influence of fixative concentration on post-mortem T2 maps using a Kinetic Tensor model