Birkl Christoph, Langkammer Christian, Golob-Schwarzl Nicole, Leoni Marlene, Haybaeck Johannes, Goessler Walter, Fazekas Franz, Ropele Stefan
Department of Neurology, Medical University of Graz, Austria.
MGH Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Harvard Medical School, Boston, MA, USA.
NMR Biomed. 2016 Apr;29(4):458-65. doi: 10.1002/nbm.3477. Epub 2016 Feb 2.
Post-mortem MRI of the brain is increasingly applied in neuroscience for a better understanding of the contrast mechanisms of disease induced tissue changes. However, the influence of chemical processes caused by formalin fixation and differences in temperature may hamper the comparability with results from in vivo MRI. In this study we investigated how formalin fixation and temperature affect T1, T2 and T2* relaxation times of brain tissue. Fixation effects were examined with respect to changes in water content and crosslinking. Relaxometry was performed in brain slices from five deceased subjects at different temperatures. All measurements were repeated after 190 days of formaldehyde immersion. The water content of unfixed and fixed tissue was determined using the wet-to-dry ratio following drying. Protein weight was determined with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Fixation caused a strong decrease of all relaxation times, the strongest effect being seen on T1, with a reduction of up to 76%. The temperature coefficient of T1 was lower in the fixed than unfixed tissue, which was in contrast to T2, where an increase of the temperature coefficient was observed following fixation. The reduction of the water content after fixation was in the range of 1-6% and thus not sufficient to explain the changes in relaxation time. Results from SDS-PAGE indicated a strong increase of the protein size above 260 kDa in all brain structures examined. Our results suggest that crosslinking induced changes of the macromolecular matrix are responsible for T1 shortening and a decreased temperature dependency. The relaxation times provided in this work should allow optimization of post-mortem MRI protocols for the brain.
脑死后磁共振成像（MRI）在神经科学领域的应用日益广泛，有助于更好地理解疾病引起的组织变化的对比机制。然而，福尔马林固定引起的化学过程以及温度差异可能会影响与活体MRI结果的可比性。在本研究中，我们调查了福尔马林固定和温度如何影响脑组织的T1、T2和T2*弛豫时间。研究了固定对水分含量变化和交联的影响。在不同温度下对五名死者的脑切片进行了弛豫测量。甲醛浸泡190天后重复所有测量。使用干燥后的湿干比测定未固定和固定组织的水分含量。通过十二烷基硫酸钠聚丙烯酰胺凝胶电泳（SDS-PAGE）测定蛋白质重量。固定导致所有弛豫时间大幅缩短，对T1的影响最为显著，最多可降低76%。固定组织中T1的温度系数低于未固定组织，这与T2相反，固定后T2的温度系数有所增加。固定后水分含量的降低在1%-6%范围内，因此不足以解释弛豫时间的变化。SDS-PAGE结果表明，在所检查的所有脑结构中，分子量大于260 kDa的蛋白质显著增加。我们的结果表明，交联引起的大分子基质变化是T1缩短和温度依赖性降低的原因。本研究提供的弛豫时间应有助于优化脑死后MRI方案。
