A longitudinal study to characterize quantitative MRI changes due to progressive formalin-fixation in whole postmortem human brains
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Abstract
Postmortem MRI can be used to reveal important pathologies and establish radiology-pathology correlations. However, quantitative MRI values are altered by tissue fixation. Therefore, the purpose of this thesis was to investigate time-dependent effects of formalin fixation on MR relaxometry (T1 and T2), diffusion tensor (fractional anisotropy, FA; and mean diffusivity, MD), and myelin water fraction (MWF) measurements throughout intact human brain specimens. Two whole, neurologically-healthy human brains were immersed in 10% formalin solution and then scanned at 13 time-points between 0 and 1032 hours. Whole brain maps of longitudinal (T1) and transverse (T2) relaxation times, FA, MD, and MWF were generated at each time-point to illustrate the changes over time, and region-of-interest analyses were performed in eight brain structures to quantify the changes with progressive fixation.Although neither of the diffusion measures (FA nor MD) showed significant changes as a function of formalin fixation, both T1 and T2-relaxation times were significantly decreased, and MWF estimates were significantly increased. These results suggest that T1-relaxation, T2-relaxation and myelin water fraction estimates must be performed very early, or at consistent time-points, in the fixation process to avoid formalin-induced changes compared to in vivo values or between samples, respectively.