Department of Radiology, Washington University in St. Louis, 4525 Scott Ave. Room 3216, St. Louis, MO 63110, United States.
Department of Radiology, The First Affiliated Hospital of USTC, Hefei, Anhui 230001, China.
Neuroimage. 2021 Jul 15;235:118012. doi: 10.1016/j.neuroimage.2021.118012. Epub 2021 Apr 8.
Non-heme iron is an important element supporting the structure and functioning of biological tissues. Imbalance in non-heme iron can lead to different neurological disorders. Several MRI approaches have been developed for iron quantification relying either on the relaxation properties of MRI signal or measuring tissue magnetic susceptibility. Specific quantification of the non-heme iron can, however, be constrained by the presence of the heme iron in the deoxygenated blood and contribution of cellular composition. The goal of this paper is to introduce theoretical background and experimental MRI method allowing disentangling contributions of heme and non-heme irons simultaneously with evaluation of tissue neuronal density in the iron-rich basal ganglia. Our approach is based on the quantitative Gradient Recalled Echo (qGRE) MRI technique that allows separation of the total R2 metric characterizing decay of GRE signal into tissue-specific (R2t) and the baseline blood oxygen level-dependent (BOLD) contributions. A combination with the QSM data (also available from the qGRE signal phase) allowed further separation of the tissue-specific R2t metric in a cell-specific and non-heme-iron-specific contributions. It is shown that the non-heme iron contribution to R2t relaxation can be described with the previously developed Gaussian Phase Approximation (GPA) approach. qGRE data were obtained from 22 healthy control participants (ages 26-63 years). Results suggest that the ferritin complexes are aggregated in clusters with an average radius about 100nm comprising approximately 2600 individual ferritin units. It is also demonstrated that the concentrations of heme and non-heme iron tend to increase with age. The strongest age effect was seen in the pallidum region, where the highest age-related non-heme iron accumulation was observed.
非血红素铁是支持生物组织结构和功能的重要元素。非血红素铁的失衡会导致不同的神经紊乱。已经开发了几种基于 MRI 信号弛豫特性或测量组织磁化率的铁定量方法。然而，由于去氧血液中的血红素铁和细胞成分的贡献，非血红素铁的特异性定量可能受到限制。本文的目的是介绍理论背景和实验性 MRI 方法，该方法允许同时分离血红素和非血红素铁的贡献，同时评估富含铁的基底神经节中的组织神经元密度。我们的方法基于定量梯度回波（qGRE）MRI 技术，该技术允许将表征 GRE 信号衰减的总 R2 度量分解为组织特异性（R2t）和基线血氧水平依赖（BOLD）贡献。与 QSM 数据（也可从 qGRE 信号相位获得）相结合，允许进一步分离组织特异性 R2t 度量的细胞特异性和非血红素铁特异性贡献。结果表明，非血红素铁对 R2t 弛豫的贡献可以用先前开发的高斯相位逼近（GPA）方法来描述。从 22 名健康对照参与者（年龄 26-63 岁）中获得 qGRE 数据。结果表明，铁蛋白复合物以平均半径约为 100nm 的簇形式聚集，包含大约 2600 个单个铁蛋白单位。还证明了血红素和非血红素铁的浓度随着年龄的增长而增加。在苍白球区域观察到最强的年龄效应，在该区域观察到与年龄相关的非血红素铁积累最高。
