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.研究目的 采用脱谐饱和（Off-Resonance Saturation, ORS）方法检测铁蛋白结合铁池——该物质作为可反映细胞铁状态的内源性对比剂，能够提供细胞铁状态相关信息。 研究方法 本研究在7T临床前磁共振扫描仪上实施了ORS采集协议，并将对比图像拟合至已确立的分析模型。通过对含铁蛋白的体模开展相关性分析与Bland-Altman分析，完成了该方法的有效性验证。针对以脑铁蓄积为特征的神经系统疾病（即阿尔茨海默病、亨廷顿病及铜蓝蛋白缺乏症）患者的死后脑组织，我们获取了铁蛋白-铁映射图像，并通过组织学染色完成验证。此外，还获取了横向弛豫率与磁化率值以作对比分析。 研究结果 在所有纳入病例的死后脑组织中，铁蛋白-铁对比度均与组织学铁染色结果呈现高度共定位。通过ORS方法获取的定量铁含量数值与现有文献报道结果一致。 研究结论 脱谐饱和方法可在减轻髓鞘信号干扰的同时，有效检测灰质结构中的铁含量。若脑组织中存在低铁参考区域，该方法可生成定量铁映射图像。本方法适用于脑铁蓄积相关脑部疾病的研究，可作为现有铁敏感参数化成像方法的有效补充。