Off-resonance saturation as an MRI method to quantify ferritin-bound iron in the post-mortem brain

Purpose
To employ an Off-Resonance Saturation (ORS) method to measure the ferritin-bound iron pool, which is an endogenous contrast agent which can give information on cellular iron status.
Methods
An ORS acquisition protocol was implemented on a 7T preclinical scanner and the contrast maps were fitted to an established analytical model. The method was validated by correlation and Bland-Altman analysis on a ferritin-containing phantom. Ferritin-iron maps were obtained from post-mortem tissue of patients with neurological diseases characterized by brain iron accumulation, i. e. Alzheimer’s disease, Huntington’s disease and aceruloplasminemia, and validated with histology. Transverse relaxation rate and magnetic susceptibility values were also obtained for comparison.
Results
In post-mortem tissue, the ferritin-iron contrast strongly co-localizes with histological iron staining, in all the cases. Quantitative iron values obtained via the ORS method are in agreement with literature.
Conclusions
Off-resonance saturation is an effective way to detect iron in grey matter structures, while mitigating for the presence of myelin. If a reference region with little iron is available in the tissue, the method can produce quantitative iron maps. This method is applicable in the study of brain diseases characterized by brain iron accumulation and complement existing iron-sensitive parametric methods.

目的

旨在采用离谐饱和（ORS）技术以测量铁蛋白结合的铁库，该铁库作为一种内源性对比剂，能够提供有关细胞铁状态的详细信息。

方法

在7T临床前扫描仪上实施ORS采集方案，并将对比图与已建立的解析模型进行拟合。通过对比含有铁蛋白的模型进行相关性验证和Bland-Altman分析以验证该方法。从具有脑铁积累特征的神经疾病患者（如阿尔茨海默病、亨廷顿病和血铜蓝蛋白尿症）的尸体组织中获得铁蛋白-铁图，并通过组织学验证。同时，还获得了横向弛豫率和磁化率值以供比较。

结果

在尸体组织中，铁蛋白-铁对比剂在所有病例中均与组织学铁染色强共定位。通过ORS方法获得的定量铁值与文献中的数据一致。

结论

离谐饱和是一种有效的检测灰质结构中铁的方法，同时可减轻髓鞘存在的影响。若组织中存在铁含量较少的参考区域，该方法可生成定量铁图。此方法适用于研究以脑铁积累为特征的脑部疾病，并补充现有的铁敏感性参数方法。