Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla
Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla
复制标题
DOI：
10.1093/brain/awr278
复制
发表时间：
2011-12-01
期刊：
影响因子：
14.5
通讯作者：
Duyn, Jeff H.
中科院分区：
文献类型：
--
作者：
Bagnato, Francesca;Hametner, Simon;Duyn, Jeff H.
以前的作者已经证明，磁共振成像中表征梯度回波信号衰减的横向弛豫度R-2*和频移与大脑白质中铁和髓鞘的分布密切相关。在多发性硬化症中，脑组织中铁的积聚可能反映了多种病理过程。因此，铁可能具有作为疾病病理的体内磁共振成像示踪剂的独特潜力。为了探讨铁对多发性硬化症病理变化的跟踪能力，我们在7特斯拉的梯度回波磁共振成像上对白质病变和外观不同的正常白质区域进行了定性的组织病理学分析。本研究使用的样本来自两名多发性硬化症患者和一名非多发性硬化症捐赠者。磁共振图像是使用全身7特斯拉磁共振成像扫描仪采集的，该扫描仪配备了专为组织成像设计的24通道仅接收阵列。获得了三维多梯度回波序列，并重建了定量的R-2*图和相位图。3~5 mm厚石蜡切片进行髓鞘和少突胶质细胞、小胶质细胞和巨噬细胞、铁蛋白和铁蛋白轻多肽的免疫组织化学染色。用Perl‘s染色和3，3’-二氨基联胺-四盐酸盐增强特恩布尔蓝染色检测铁。在多发性硬化症组织中，铁的存在总是伴随着R-2*的增加。相反，在组织化学染色中，R-2*的增加并不总是与铁的存在相关。我们将这一发现解释为包埋、切片和染色过程的影响。这些过程可能会影响组织病理学分析结果，但不会影响组织操作前获得的磁共振成像。确定了铁的几种细胞来源。这些来源包括正常白质中的少突胶质细胞和白质病变边缘激活的巨噬细胞/小胶质细胞。此外，在白质病变中，Perl‘s染色显示典型的微出血聚集体中铁沉淀。我们的联合成像和病理研究表明，多梯度回波磁共振成像是识别多发性硬化症患者脑组织中铁的一种敏感技术。然而，磁共振成像确定的铁不一定反映病理，也可能在表面上正常的组织中看到。通过多梯度回波磁共振成像识别病变组织中的铁，结合地形信息和患者病史，可以揭示病理过程。
Previous authors have shown that the transverse relaxivity R-2* and frequency shifts that characterize gradient echo signal decay in magnetic resonance imaging are closely associated with the distribution of iron and myelin in the brain's white matter. In multiple sclerosis, iron accumulation in brain tissue may reflect a multiplicity of pathological processes. Hence, iron may have the unique potential to serve as an in vivo magnetic resonance imaging tracer of disease pathology. To investigate the ability of iron in tracking multiple sclerosis-induced pathology by magnetic resonance imaging, we performed qualitative histopathological analysis of white matter lesions and normal-appearing white matter regions with variable appearance on gradient echo magnetic resonance imaging at 7 Tesla. The samples used for this study derive from two patients with multiple sclerosis and one non-multiple sclerosis donor. Magnetic resonance images were acquired using a whole body 7 Tesla magnetic resonance imaging scanner equipped with a 24-channel receive-only array designed for tissue imaging. A 3D multi-gradient echo sequence was obtained and quantitative R-2* and phase maps were reconstructed. Immunohistochemical stainings for myelin and oligodendrocytes, microglia and macrophages, ferritin and ferritin light polypeptide were performed on 3- to 5-mu m thick paraffin sections. Iron was detected with Perl's staining and 3,3'-diaminobenzidine-tetrahydrochloride enhanced Turnbull blue staining. In multiple sclerosis tissue, iron presence invariably matched with an increase in R-2*. Conversely, R-2* increase was not always associated with the presence of iron on histochemical staining. We interpret this finding as the effect of embedding, sectioning and staining procedures. These processes likely affected the histopathological analysis results but not the magnetic resonance imaging that was obtained before tissue manipulations. Several cellular sources of iron were identified. These sources included oligodendrocytes in normal-appearing white matter and activated macrophages/microglia at the edges of white matter lesions. Additionally, in white matter lesions, iron precipitation in aggregates typical of microbleeds was shown by the Perl's staining. Our combined imaging and pathological study shows that multi-gradient echo magnetic resonance imaging is a sensitive technique for the identification of iron in the brain tissue of patients with multiple sclerosis. However, magnetic resonance imaging-identified iron does not necessarily reflect pathology and may also be seen in apparently normal tissue. Iron identification by multi-gradient echo magnetic resonance imaging in diseased tissues can shed light on the pathological processes when coupled with topographical information and patient disease history.