The influence of brain iron and myelin on magnetic susceptibility and effective transverse relaxation - A biochemical and histological validation study

The influence of brain iron and myelin on magnetic susceptibility and effective transverse relaxation - A biochemical and histological validation study
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DOI:
10.1016/j.neuroimage.2018.06.007
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发表时间:
2018-10-01
期刊:
影响因子:
5.7
通讯作者:
Grabner, Guenther
Grabner, Guenther
中科院分区:
医学1区
文献类型:
--
作者:
Hametner, Simon;Endmayr, Verena;Grabner, Guenther

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定量磁化率图(QSM)和有效横向弛豫速率图(R2*)对脑铁含量的变化高度敏感。临床磁共振成像(MRI)研究报告了各种神经系统疾病的易感性和松弛率的变化,这通常被等同于局部脑铁含量的变化。然而,这些提到的指标缺乏铁的特异性,因为它们也受到髓鞘存在的影响。在这项研究中,我们评估了QSM和R2*反映铁浓度以及组织学铁和髓鞘强度的程度。用7T磁共振扫描仪对6例未固定的人死后脑进行原位成像。福尔马林固定后,取脑轴位切片,打孔。对671个组织冲床进行亚铁锌铁的定量测定。随后,脑片石蜡包埋,组织学双侧大脑半球轴位切片分别进行豪华坚牢蓝(髓鞘)和二氨基联苯胺(DAB)增强的特恩布尔蓝(铁)染色。在组织学染色上绘制3331个感兴趣区(ROI),以评估髓鞘和铁的强度,并与相应ROI的MRI数据进行比较。QSM更能反映铁锌铁的定量(r=0.755比0.738),而R2*与铁染色强度有更好的相关性(r=0.619比0.445)。髓鞘强度与Qsm呈负相关(r=-0.352),提示髓鞘对敏感性有抗磁性作用。丘脑髓鞘密度高于基底节。尽管如此,在定量铁值和QSM之间仍然观察到了显著的关系,证实了后者在这个大脑区域对铁的量化的适用性。
Quantitative susceptibility mapping (QSM) and effective transverse relaxation rate (R2*) mapping are both highly sensitive to variations in brain iron content. Clinical Magnetic Resonance Imaging (MRI) studies report changes of susceptibilities and relaxation rates in various neurological diseases which are often equated with changes in regional brain iron content. However, these mentioned metrics lack specificity for iron, since they are also influenced by the presence of myelin. In this study, we assessed the extent to which QSM and R2* reflect iron concentration as well as histological iron and myelin intensities. Six unfixed human post-mortem brains were imaged in situ with a 7 T MRI scanner. After formalin fixation, the brains were sliced axially and punched. 671 tissue punches were subjected to ferrozine iron quantification. Subsequently, brain slices were embedded in paraffin, and histological double-hemispheric axial brain slices were stained for Luxol fast blue (myelin) and diaminobenzidine (DAB)-enhanced Turnbull blue (iron). 3331 regions of interest (ROIs) were drawn on the histological stainings to assess myelin and iron intensities, which were compared with MRI data in corresponding ROIs. QSM more closely reflected quantitative ferrozine iron values (r = 0.755 vs. 0.738), whereas R2* correlated better with iron staining intensities (r = 0.619 vs. 0.445). Myelin intensities correlated negatively with QSM (r = -0.352),indicating a diamagnetic effect of myelin on susceptibility. Myelin intensities were higher in the thalamus than in the basal ganglia. A significant relationship was nonetheless observed between quantitative iron values and QSM, confirming the applicability of the latter in this brain region for iron quantification.