Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford.
Department of Radiology, University of Chicago, Chicago, Illinois, USA.
Hum Brain Mapp. 2021 Dec 15;42(18):5956-5972. doi: 10.1002/hbm.25661. Epub 2021 Sep 20.
Formalin fixation has been shown to substantially reduce T 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 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 inhomogeneity. To achieve this, T 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 pattern consistent with modelled fixative outflux. Confound regression of fixative concentration reduced T 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 and ferritin/myelin proteolipid protein (PLP) histology lead to an increased similarity for the relationship between R and PLP for the two fixative types after KT correction.
福尔马林固定已被证明会大大降低 T 值的估计，主要是由于组织中固定剂的存在。在扫描之前，通常将死后样本放入具有更有利的成像特性的液体中。本研究调查了由于固定剂流出到周围液体中，是否会导致靠近组织表面的区域中的 T 值发生变化。此外，我们还研究了是否可以使用模拟的固定剂浓度空间图作为混杂回归项来减少 T 值的不均匀性。为此，在扫描前约 48 小时，将 14 个完整的福尔马林固定的死后大脑放入 Fluorinert 中，获得了 T 图谱和扩散张量估计。其中 7 个大脑用 10%福尔马林固定，7 个大脑用 10%中性缓冲福尔马林（NBF）固定。固定剂流出使用拟议的动力学张量（KT）模型进行建模，该模型结合了体素扩散张量估计，以考虑扩散各向异性和组织特异性扩散系数。用 10% NBF 固定的大脑显示出与模型化固定剂流出一致的空间 T 模式。混杂回归固定剂浓度降低了白质和灰质的 T 值不均匀性，与简单的固定剂流出模型相比，KT 模型的降低幅度最大。用 10%福尔马林固定的大脑则没有观察到这种效果。横向弛豫率 R 与铁蛋白/髓鞘蛋白脂蛋白（PLP）组织学之间的相关性导致在 KT 校正后，两种固定剂类型之间 R 和 PLP 之间的关系更加相似。
