Longitudinal whole-human-brain quantitative MRI study on autolysis, fixation, rehydration, and shrinkage effects

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Abstract
Post mortem MRI studies of formalin-fixed brain tissue are essential for linking in vivo MRI contrast to underlying microstructure measured with ex vivo histology, yet formalin not only preserves tissue but also systematically alters MRI-relevant physical properties. To systematically quantify and model these effects, we longitudinally characterized multi-parametric mapping (MPM) measures — longitudinal (R 1 ) and effective transverse (R 2 *) relaxation rates, proton density proxy (N A ), and magnetization transfer saturation ratio (MT sat ) — across the different post mortem processes, i.e. autolysis, fixation, and hydration. Five whole-human brains were scanned longitudinally during fixation (and in situ -after rehydration, when available), and compared with an independent in vivo cohort of 25 younger healthy participants. Each MPM parameter followed a distinct trajectory across different post mortem processes. The largest changes were found for R 1 during fixation relative to in situ values (more than 250%), followed by R 2 * with an almost 60% increase, and MT sat with a 26% reduction from in vivo to in situ . N A showed no detectable change during fixation. We developed models describing fixation-induced changes and tissue shrinkage. The R 1 changes and tissue shrinkage were closely aligned, reflecting a likely common mechanism. MT sat largely preserved tissue contrast during fixation and rehydration, supporting its use for spatial alignment between in vivo MRI, fixed-tissue MRI, and histology. With our quantitative assessment of post mortem process-dependent changes we provide a unique resource for future studies to better link in vivo to fixed post mortem MRI data and thereby bridge the gap to ex vivo histology.

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